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Channels Product Listing | Edition 1

Western Honey Bee Apis mellifera A source of Apamin

Products by Gating Mechanism: • Ligand-gated Ion Channels • Voltage-gated Ion Channels • Other Ion Channels Tocris Product Listing Series Introduction Ion channels are pore-forming present in the plasma membrane of most cells, as well as the intracellular membranes surrounding many organelles, allowing the passage of across the membrane. They are essential for maintaining resting , generating action potentials and other electrical signaling, and regulating volume. Ion channels have a fundamental role in physiological processes such as activation, , release from pancreatic β cells and transport of nutrients and ions across epithelial cells. A huge variety of ion channels exist, exhibiting selective permeability to particular ions and having different gating mechanisms. Ion channels may be classified according to their ion selectivity or gating mechanism, i.e. how the flow of ions is controlled. We have followed the IUPHAR classification of ion channels for the purposes of this listing and grouped the products into three main sections according to gating mechanism: Ligand-gated Ion Channels, Voltage- gated Ion Channels, and Other Channels.

Contents

Ligand-gated Ion Channels 3 Channels 17 Ca2+-Activated Potassium Channels 17 5-HT3 4 Inward Rectifier Potassium (K ) Channels 18 Nicotinic Receptors 4 ir Two-P Potassium Channels 19 Nicotinic (α7) Receptors 4 Voltage-gated Potassium (Kv) Channels 19 Nicotinic (α4β2) Receptors 6 Non-selective / Other Potassium Channels 19 Nicotinic Receptors (Non-selective/Other) 7 Sodium Channels 20 Acid-sensing Ion Channels 8 Voltage-gated Sodium Channels 20 Epithelial Sodium Channels 8 Transient Potential Channels 20 GABA and GABA Receptors 8 A A-ρ TRPA1 20 GABA Receptors 8 A TRPC 20 GABA Receptors 9 A-ρ TRPM 20 GABA Miscellaneous 9 TRPML 21 Glutamate (Ionotropic) Receptors 9 TRPP 21 AMPA Receptors 9 TRPV 21 Kainate Receptors 10 The Comprehensive in Vitro Proarrhythmia 23 NMDA Receptors 10 Assay Initiative (CiPA) Other Glutamate 12 Receptors 13 Other Channels 24 HCN Channels 13 24

IP3 Receptors 13 Chloride Channels 24 Purinergic (P2X) Receptors 13 -activated Chloride Channels 24 CFTR 24 Voltage-gated Ion Channels 15 Other Chloride Channels 24 Calcium Channels 16 Ionophores 24 Receptors 16 Photoswitchable Ligands 25 STIM-Orai Channels 16 Other Channel Modulators 25 Voltage-gated Calcium Channels 16 Other Calcium Channels 17 Antibodies Targeting Ion Channels 26 References 27

Front cover image by Mikhail Laptev (https://www.dreamstime.com/royalty-free-stock-photography-honey-bee-apis-mellifera-dahlia-flower-image27164717) via dreamstime.com

2 | ion channels Ligand-gated Ion Channels Ligand-gated ion channels are a large group of transmembrane proteins that allow the passage of ions through the membrane in response to the binding of a specific chemical messenger; they are also known as ionotropic receptors. Ligand-gated ion channels are grouped according to the endogenous compound to which they selectively respond; these include 5-HT, ATP, GABA, glutamate, acetylcholine and glycine. In general, the binding site for the ligand is distinct from the pore, and binding results in either channel opening or closing.

Figure 1 | A representation of the ligand-gated tree featuring of ion channels targeted by Tocris products

P2X ENaC P2RX1 P2RX6 SCNN1A P2RX2 SCNN1D P2RX4 SCNN1B P2RX5 P2RX7 SCNN1G P2RX3

ASIC2 ASIC1 ASIC ASIC3 ASIC4

ASIC5

GRIN2D GRIN2C GRIN3B NMDA GRIN2B GRIN1 GRIN3A GRIN2A

GRIK5

GRIK4 GRIK3

GRIK2 Kainate

GRIA4 GRIK1 GRIA2 GRIA3 AMPA GRIA1 CHRNA9 CHRNG nAChR CHRNA10 CHRNE CHRNB4 CHRND CHRNB2 CHRNB3 CHRNA7 CHRNB1 CHRNA CHRNA6 CHRNA3 CHRNA4 CHRNA1 CHRNA2 HTR3E HTR3C Gene Ion Channel 5-HT abbreviation HTR3D ASIC acid-sensing ion channel HTR3B CHRNA receptor nicotinic alpha subunit HTR3A CHRNB cholinergic receptor nicotinic beta subunit CHRND cholinergic receptor nicotinic delta subunit GABRG2 GLRA3 CHRNE cholinergic receptor nicotinic epsilon subunit GLRA1 CHRNG cholinergic receptor nicotinic gamma subunit GABRG1 GABRA γ-aminobutyric acid type A receptor alpha subunit GLRA2 GABRB γ-aminobutyric acid type A receptor beta subunit GABRG3 GlyR GABRD γ-aminobutyric acid type A receptor delta subunit GABRE GLRA4 GABRE γ-aminobutyric acid type A receptor epsilon GABRR2 GLRB subunit GABRB1 GABRR1 GABRG γ-aminobutyric acid type A receptor gamma GABRQ subunit GABRR3 GABRB3 GABRP γ-aminobutyric acid type A receptor pi subunit GABRP GABRQ γ-aminobutyric acid type A receptor theta subunit GABRA6 GABRR γ-aminobutyric acid type A receptor rho subunit GABRB2 GABRD GRIA glutamate ionotropic receptor AMPA type subunit GRIK glutamate ionotropic receptor kainate type GABRA4 subunit GRIN glutamate ionotropic receptor NMDA type subunit GABRA2 GABAa GLRA alpha GABRA1 GLRB glycine receptor beta GABRA3 GABRA5 HTR3 5-hydroxytryptamine receptor 3 P2RX P2X SCNN epithelial (ENaC) Adapted from www.guidetopharmacology.org

www.tocris.com | 3 Tocris Product Listing Series

Category Cat. No. Product Name Description Unit Size

5-HT3

Agonists 0440 m-Chlorophenylbiguanide Potent and specific 5-HT3 100 mg

0558 2-Methyl-5-hydroxytryptamine 5-HT3 agonist/potent 5-HT6 ligand 10 mg 50 mg

0566 N-Methylquipazine 5-HT3 agonist 100 mg

0629 Quipazine 5-HT3 agonist 100 mg

0988 RS 56812 5-HT3 10 mg 50 mg 3547 Endogenous 5-HT receptor agonist 50 mg

1205 SR 57227 Potent, selective 5-HT3 agonist 10 mg 50 mg

Antagonists 0666 3-AQC 5-HT3 antagonist 10 mg 50 mg

2759 B-HT 920 5-HT3 antagonist; also α2 agonist and D2 receptor agonist 10 mg 50 mg 0475 Non-selective 5-HT antagonist; also partial α agonist 100 mg

5629 Dolasetron Potent and selective 5-HT3 antagonist 10 mg 50 mg

2903 Granisetron 5-HT3 antagonist 10 mg 50 mg

0640 MDL 72222 5-HT3 antagonist 50 mg

2018 5-HT3, 5-HT2, H1 and α2-antagonist; 10 mg 50 mg

2844 Mosapride citrate 5-HT3 antagonist and 5-HT4 agonist 10 mg 50 mg

2891 Ondansetron Selective 5-HT3 antagonist 10 mg 50 mg

2037 SDZ 205-557 5-HT3 and 5-HT4 10 mg 50 mg

0641 Tropanyl-3,5-dimethylbenzoate 5-HT3 antagonist 100 mg

2459 Potent 5-HT3 receptor antagonist; also partial agonist of α7 nAChR 10 mg 50 mg

4532 VUF 10166 High affinity 5-HT3 receptor antagonist 10 mg 50 mg

0380 Y-25130 Potent, selective 5-HT3 antagonist 10 mg 50 mg

1795 Zacopride Highly potent 5-HT3 receptor antagonist; also 5-HT4 agonist 10 mg 50 mg Acetylcholine Nicotinic Receptors Nicotinic (α7) Receptors 4234 4BP-TQS Allosteric agonist at α7 nAChR 10 mg 4341 A 582941 Partial agonist at α7 nAChR 10 mg 50 mg 4477 A 844606 Selective α7 nAChR partial agonist 10 mg 50 mg 2809 Acetylcholine Endogenous 50 mg 3964 AR-R 17779 α7-selective agonist 10 mg 2241 DMAB- Partial agonist at α7 nAChR; also α4β2 antagonist 10 mg 50 mg 4557 GTS 21 Partial agonist at α7 nAChR 10 mg 50 mg 3092 PHA 543613 Potent and selective α7 nAChR agonist 10 mg 3134 PHA 568487 α7-selective agonist 10 mg 50 mg 2303 PNU 282987 Selective α7 nAChR agonist 10 mg 50 mg

4 | ion channels Ligand-gated Ion Channels – continued

Ion Channels in Immunology Research T and B cells and microglia express a wide variety of ion channels, which are implicated in immune processes. Below is a selection of compounds from Tocris that may be used to explore the role of ion channels in the immune system.

N N OMe N N N N N Cl O NaO3S

Cl

O NaO3S

NaO3S HN A 438079 (2972) OMe HN SO3Na Competitive P2X7 receptor antagonist

P2X7 receptors expressed on T cells and O microglia are associated with cell migration, SKF 96365 (1147) Inhibits STIM1-mediated Ca2+ HN proliferation, and release as well as O Th17 differentiation. influx; also TRPC channel inhibitor HN Calcium is a second messenger in O lymphocytes, regulating proliferation, , motility and other functions. STIM1 is the putative Ca2+ sensor on the HN SO3Na (ER). NaO3S HN

O NaO3S

O S N NaO3S N Cl O NF 449 (1391) N N Potent and selective P2X H H 1 receptor antagonist TRAM 34 (2946) OH P2X1 receptors are expressed on Potent and highly selective KCa 3.1 5J 4 (5490) T cells and are associated activation. CRAC channel blocker; blocks Potassium channels regulate the membrane store-operated calcium entry

potential of lymphocytes and KCa3.1 CRAC channels are expressed in channels are associated with membrane lymphocytes and are activated in response hyperpolarization in response to elevated to depleted intracellular Ca2+ stores. 2+ intracellular Ca levels. 2+ Ca release from ER is triggered by IP3 in response to receptor activation.

Category Cat. No. Product Name Description Unit Size 1271 RJR 2429 Nicotinic receptor agonist 10 mg Immunology feature products 50 mg 3518 S 24795 Partial agonist at α7 nAChR 10 mg 50 mg

4441 SEN 12333 α7 nAChR agonist; H3 antagonist 10 mg 50 mg 5559 SSR 180711 Partial agonist at α7 nAChR 10 mg 50 mg 2518 TC 1698 α7-selective agonist 10 mg 50 mg Antagonists 2133 α- α7 subtype-selective nAChR antagonist 1 mg 3119 α- ImI α7 and α9 selective nAChR antagonist 500 μg 3405 COG 133 Nicotinic α7 antagonist; ApoE fragment 1 mg 1029 α7 neuronal nicotinic receptor antagonist 5 mg 25 mg 1356 MG 624 α7 neuronal nicotinic receptor antagonist 10 mg 50 mg Modulators 4571 A 867744 Positive of α7 nAChR 10 mg 50 mg 3837 CCMI Positive allosteric modulator of α7 nAChR 10 mg 50 mg 1260 Allosteric modulator of α7 nicotinic receptors 100 mg

www.tocris.com | 5 Tocris Product Listing Series

Pentameric nAChR with central cation channel Subunit topography and notional sites for interactions K+ N

ACh Agonist/competitive binding nd C antagonist binding site 2 agonist/competitive (AChBP) C at subunit interface antagonist site Cys-loop C Out Allosteric modulator sites

M1 M2 M3 M4

In Channel blocker/ non-competitive antagonist M2 lines the cation channel

Ca2+, Na+

Left: The topography of a single nAChR subunit. The two residues forming the signature cys-loop are indicated. The extracellular N-terminal domain corresponds to the AChBP. Right: Schematic of a generic nAChR showing 5 subunits spanning the membrane to form a central ion channel. Notional sites of action of interacting are shown: two agonist binding sites are indicated at extracellular subunit interfaces, consistent with a heteromeric nAChR. Competitive antagonist sites overlap the agonist binding sites. Extracellular and intramembrane sites have been proposed for different allosteric modulators. Non-competitive antagonists may occlude or block the ion channel, as indicated, or may act at other sites. See text for further details.

Category Cat. No. Product Name Description Unit Size

4141 LY 2087101 Potentiator of α7 nAChRs 10 mg 50 mg 2995 NS 1738 Positive allosteric modulator of α7 nAChR; active in vivo 10 mg 50 mg 2498 PNU 120596 Positive allosteric modulator of α7 nAChR; active in vivo 10 mg 50 mg 4233 TQS Positive allosteric modulator of α7 nAChRs 10 mg 50 mg Other 5156 Ivermectin B1a-d2 Deuterated ivermectin B1a (Cat. No. 1260) 1 mg Nicotinic (α4β2) receptors Agonists 5017 A 85380 High affinity and selectiveα 4β2 agonist 10 mg 5079 ABT 089 High affinity and selectiveα 4β2 partial agonist 10 mg 50 mg 5236 CC4 High affinity and subtype-selectiveα 6β2 and α4β2 partial agonist 10 mg 50 mg 4125 3-pyr- High affinity, partial agonist ofα 4β2 receptors 10 mg 50 mg 5557 Selective α4β2 nAChR partial agonist 10 mg 50 mg 1518 5-Iodo-A-85380 High affinityα 4β2 and α6β2 subtype-selective agonist 10 mg 1527 5-Iodo-A-85380, 5-trimethylstannyl N-BOC Precursor to 5-Iodo-A-85380 (Cat. No. 1518) 200 μg derivative 1053 RJR 2403 α4β2 selective 10 mg 50 mg 2737 TC 2559 Selective partial agonist at α4β2 receptors 10 mg 50 mg 3754 Orally active, subtype-selective α4β2 partial agonist 10 mg 50 mg

6 | ion channels Ligand-gated Ion Channels – continued

Human α4β2 Nicotinic Receptor X-Ray crystal structure of α4β2 nicotinic receptor in complex with

Cat. No. 3546 N Cat. No. 3546 N

• Nicotine is the prototypical nAChR agonist (Ki = 1 nM) • The effects of nicotine in the , including its reinforcing properties that lead to , are mediated by α4β2 receptors Image adapted from RSCB (http://www.rcsb.org). PDB ID: 5KXI Morales-Perez et al. (2016) 538 411. • Nicotine binds in the classical neurotransmitter site at PMID 27698419. the α–β interface. MeHN O N O N O Category Cat. No. Product Name Description Cat.Unit No. Size 2555 .HCI Modulators 3328 Positive allosteric modulator of α4β2; also muscle-type nAChR 10 mg inhibitor 50 mg

5112 NS 9283 Positive allosteric modulatorO of α4β2 10 mg 50 mg Other 2736 Sazetidine A α4β2 receptor ligand; may act as an agonist or a desensitizer 10 mg Nicotinic Receptors (Non-selective/Other) Agonists 0351 1-Acetyl-4-methylpiperazine Nicotinic agonist 10 mg 50 mg 0352 4-Acetyl-1,1-dimethylpiperazinium Nicotinic agonist 10 mg 50 mg 1971 (+)- Neuronal nicotinic receptor partial agonist 50 mg 0789 (±)-Anatoxin A Nicotinic agonist 1 mg 3549 3-Bromocytisine Potent agonist of α4β4, α4β2 and α7 nACh receptors 10 mg 50 mg 2810 Carbamoylcholine Cholinergic receptor agonist 100 mg 3110 (-)- Major metabolite of nicotine 50 mg 1390 (-)-Cytisine Potent, selective neuronal nicotinic agonist 10 mg 50 mg 0684 (±)- High affinity nicotinic agonist 10 mg 1077 (-)- Nicotinic partial agonist 100 mg 3546 (-)-Nicotine Prototypical nAChR agonist 50 mg 4831 NS 3861 α3β2 full agonist; also α3β4 partial agonist 10 mg 50 mg 3855 RuBi-Nicotine Caged nicotine; rapidly excitable by visible light 10 mg 4766 SIB 1508Y Potent agonist of α4β2, α2β4, α4β4 and α3β4 nACh receptors 10 mg 50 mg 4764 SIB 1553A Subunit selective nAChR agonist 10 mg 50 mg 1348 UB 165 Subunit selective nAChR agonist 10 mg Antagonists 3205 ACV 1 α9α10-selective antagonist 100 μg 4128 Bisindolylmaleimide II Nicotinic receptor antagonist; also potent PKC inhibitor 10 mg 50 mg

www.tocris.com | 7 Tocris Product Listing Series

Category Cat. No. Product Name Description Unit Size 0424 Benzoquinonium 10 mg 50 mg 3221 bPiDDB Orthosteric nAChR antagonist 10 mg 50 mg 2722 Catestatin Non-competitive nicotinic cholinergic antagonist 1 mg 1001 Nicotinic antagonist; slow offset 10 mg 50 mg 3120 α-Conotoxin AuIB Selective α3β4 nAChR antagonist 500 μg 3124 α-Conotoxin EI α1β1δγ selective nAChR antagonist 500 μg 1340 α-Conotoxin MII Potent α3β2 and β3 subunit selective nicotinic antagonist 500 μg 3121 α-Conotoxin PIA Selective antagonist of α6-containing nicotinic receptors 500 μg 3123 α-Conotoxin PnIA Selective α3β2 nAChR antagonist 500 μg 2349 Dihydro-β-erythroidine Antagonist for neuronal α4-containing nicotinic receptors 10 mg 50 mg 4111 Nicotinic receptor blocker 50 mg 2843 Non-competitive nicotinic receptor antagonist 10 mg 50 mg 0693 Pancuronium Nicotinic (neuromuscular) antagonist 10 mg 50 mg 4424 SR 16584 Selective α3β4 nAChR antagonist 10 mg 50 mg 2438 TMPH Neuronal nicotinic receptor antagonist 10 mg 50 mg 2820 (+)-Tubocurarine Nicotinic receptor antagonist 50 mg Other 0686 Galanthamine Neuronal nicotinic receptor potentiator; also inhibitor 100 mg Acid-Sensing Ion Channels Activators 5028 GMQ Selective ASIC3 opener 10 mg 50 mg Blockers 4804 APETx2 ASIC3 channel blocker 100 μg 5938 Mambalgin 1 Selective ASIC1a inhibitor; 10 μg 5042 1 Potent and selective ASIC1a channel blocker 100 μg Epithelial Sodium Channels Activators 0464 Activator of ENaCδ; also vanilloid receptor antagonist 10 mg 50 mg Blockers 3380 Deg/ENaC channel blocker; (Cat. No. 0890) derivative; 10 mg also NCX inhibitor 50 mg

GABAA and GABAA-ρ Receptors

GABAA Receptors

Agonists 0289 Potent GABAA agonist 1 mg 10 mg 50 mg

0807 THIP GABAA agonist; also GABAA -ρ antagonist 50 mg

Antagonists 2503 (-)- methiodide -soluble GABAA antagonist 10 mg 50 mg

0109 (-)-Bicuculline methobromide Water-soluble GABAA antagonist 10 mg 50 mg

0131 (-)-Bicuculline methochloride Water-soluble GABAA antagonist 10 mg 50 mg

0130 (+)-Bicuculline Potent GABAA antagonist 50 mg

1128 GABAA receptor antagonist 1 g

1262 SR 95531 Selective, competitive GABAA receptor antagonist 10 mg 50 mg 5281 AC 5216 Selective TSPO ligand 10 mg 50 mg

1327 L-655,708 ; selective for α5-containing GABAA 10 mg receptors 50 mg

8 | ion channels Ligand-gated Ion Channels – continued

Category Cat. No. Product Name Description Unit Size 2832 Benzodiazepine agonist 10 mg 50 mg 0670 PK 11195 Antagonist at peripheral benzodiazepine receptors 10 mg 50 mg 0655 Benzodiazepine agonist 10 mg 50 mg

Modulators 3653 GABAA receptor positive allosteric modulator 10 mg

3113 Potentiator of GABAA receptors; 10 mg 50 mg 1471 GABA mimetic and GABA modulatory agent 10 mg 50 mg

2531 Ganaxolone Potent, positive allosteric modulator of GABAA receptors 10 mg 50 mg

3652 GABAA receptor positive allosteric modulator 50 mg

GABAA-ρ Receptors

Agonists 0379 SKF 97541 GABAA-ρ antagonist; also extremely potent GABAB agonist 10 mg 50 mg

0180 ZAPA Agonist at ‘low affinity’ GABAA receptor; more potent than 10 mg GABA/muscimol 50 mg

Antagonists 1040 TPMPA Selective GABAA-ρ antagonist 10 mg 50 mg GABA Miscellaneous Other 2991 DPNI-caged-GABA Nitroindoline-caged GABA 10 mg 2687 Pentylenetetrazole Convulsant 1 g 3400 RuBi-GABA Caged GABA; excitable by visible wavelength 10 mg Glutamate (Ionotropic) Receptors AMPA Receptors Antagonists 2555 GYKI 53655 Non-competitive AMPA receptor antagonist Cat. No. 3546 10 mg N 50 mg 1636 IEM 1460 Open-channel blocker of AMPA currents; selective for non-GluR2- 10 mg N containing receptors 50 mg 2345 ZK 200775 Competitive AMPA/kainate antagonist 10 mg 50 mg

AMPA-Subtype Ionotropic X-Ray crystal structure of rat GluA2 receptor in complex with the noncompetitive inhibitor GYKI 53655

MeHN O N O N O Cat. No. 2555 .HCI Cat. No. 2555

O

• GYKI 53655 is a non-competitive AMPA and kainate

receptor antagonist. IC50 is 18.9 μM for AMPA receptors. • GYKI 53655 exhibits activity. Image adapted from RSCB Protein Data Bank (http://www.rcsb.org). • The compound binds at the interface between the ion PDB ID: 5L1H Yelshanskaya et al. (2016) 91 1305. channel and the linkers connecting the transmembrane PMID 27618672 domain and the ligand-binding domain.

www.tocris.com | 9 Tocris Product Listing Series

Category Cat. No. Product Name Description Unit Size Other 6094 2R,6R- Enhances AMPA currents; metabolite of (Cat. No. 3131) 10 mg 6095 2S,6S-Hydroxynorketamine Enhances AMPA currents; metabolite of Ketamine (Cat. No. 3131) 10 mg 5982 cis-6-Hydroxynorketamine Enhances AMPA currents; metabolite of Ketamine (Cat. No. 3131) 10 mg 50 mg Kainate Receptors Agonists 0269 Potent, selective kainate agonist 1 mg 5 mg 0222 Potent excitant and 1 mg 10 mg 50 mg Antagonists 2728 ACET Potent antagonist of GluR5-containing kainate receptors 10 mg 0190 CNQX Potent AMPA/kainate antagonist 10 mg 50 mg 1045 CNQX disodium salt Potent AMPA/kainate antagonist; more water soluble form of CNQX 1 mg (Cat. No. 0190) 10 mg 50 mg 0189 DNQX Selective non-NMDA antagonist 10 mg 50 mg 2312 DNQX disodium salt Selective non-NMDA antagonist; water-soluble salt of DNQX 10 mg (Cat. No. 0189) 50 mg 3620 GluR5 antagonist; inhibits carbonic anhydrase (CA) II and IV 10 mg 50 mg 2079 UBP 302 Potent and selective kainate antagonist; active enantiomer of UBP 10 mg 296 (Cat. No. 2078) 50 mg NMDA Receptors Agonists 0186 cis-ACPD Potent NMDA agonist; also group II mGluR agonist 10 mg 50 mg 0213 d- NMDA agonist 1 g

0214 l-Aspartic acid NMDA agonist 1 g

0216 l-Cysteinesulfinic acid NMDA and mGlu agonist 100 mg 3406 GLYX 13 NMDA receptor partial agonist; acts at the glycine site 1 mg 0197 Selective, potent NMDA agonist 10 mg 50 mg 0285 Non-selective NMDA agonist 5 mg

2277 MNI-caged-d-aspartate Caged d-aspartate; NMDA agonist 10 mg 50 mg 0114 NMDA Selective NMDA agonist 50 mg 500 mg 0225 Endogenous NMDA agonist and transmitter candidate 1 g 0959 tri Agonist at polyamine site of NMDA receptor 100 mg 0312 (RS)-(Tetrazol-5-yl)glycine Highly potent NMDA receptor agonist 10 mg 50 mg Antagonists 0106 d-AP5 Potent, selective NMDA antagonist; more active form of dl-AP5 1 mg (Cat. No. 0105) 10 mg 50 mg 100 mg

0105 dl-AP5 Potent, selective NMDA antagonist 10 mg 50 mg

3693 dl-AP5 sodium salt NMDA antagonist; sodium salt of dl-AP5 (Cat. No. 0105) 10 mg 50 mg

0104 dl-AP7 Selective NMDA antagonist 10 mg 50 mg

0107 l-AP5 Potent, selective NMDA antagonist; less active form of dl-AP5 10 mg (Cat. No. 0105) 50 mg 1469 CGP 37849 Potent and selective NMDA antagonist 10 mg 50 mg

10 | ion channels Ligand-gated Ion Channels – continued

Category Cat. No. Product Name Description Unit Size 1409 CGP 39551 Potent, selective and competitive NMDA antagonist 10 mg 50 mg 1493 CGP 78608 Potent, selective glycine-site NMDA antagonist 10 mg 50 mg 1241 CGS 19755 Potent, competitive NMDA antagonist 10 mg 50 mg 0237 7-Chlorokynurenic acid NMDA receptor antagonist; also potent competitive inhibitor of 10 mg l-glutamate uptake 50 mg 3697 7-Chlorokynurenic acid sodium salt NMDA antagonist; also potent competitive inhibitor of L-glutamate 10 mg uptake; sodium salt of 7-Chlorokynurenic acid (Cat. No. 0237) 50 mg 2456 Co 101244 Highly selective NR2B antagonist 10 mg 50 mg 4136 G NR2B-selective NMDA receptor antagonist 500 μg 3125 Conantokin-R Potent non-competitive NMDA receptor antagonist 500 μg 3122 Conantokin-T Non-competitive NMDA receptor antagonist 500 μg 0247 (R)-CPP Potent NMDA antagonist; more active enantiomer of (RS)-CPP 10 mg (Cat. No. 0173) 50 mg 0173 (RS)-CPP Potent NMDA antagonist 10 mg 50 mg

1265 d-CPP-ene Potent, competitive NMDA antagonist 10 mg 0286 5,7-Dichlorokynurenic acid Potent NMDA antagonist, acts at glycine site 10 mg 50 mg 3698 5,7-Dichlorokynurenic acid sodium salt Potent NMDA antagonist, acts at glycine site; sodium salt of 10 mg 5,7-Dichlorokynurenic acid (Cat. No. 0286); 50 mg 0360 (±)-1-(1,2-Diphenylethyl) NMDA antagonist, acts at ion channel site 10 mg 50 mg 4491 DQP 1105 Selective NR2C/NR2D receptor antagonist 10 mg 50 mg 2195 Non-competitive NR2B-selective NMDA antagonist 10 mg 50 mg 2348 Potent and selective glycine site antagonist; orally available and 10 mg active in vivo 50 mg 0545 Non-competitive NMDA antagonist; also σ ligand 10 mg 50 mg 3131 Ketamine Non-competitive NMDA receptor antagonist 50 mg 4379 (S)-(+)-Ketamine NMDA receptor antagonist; enantiomer of ketamine (Cat. No. 3131) 50 mg 0742 L-689,560 Very potent NMDA antagonist 10 mg 50 mg 1019 LY 235959 Competitive NMDA antagonist 10 mg 50 mg 0773 NMDA antagonist; acts at ion channel site 50 mg 0924 (+)-MK 801 maleate Non-competitive NMDA antagonist; acts at ion channel site 10 mg 50 mg 0955 (-)-MK 801 maleate NMDA antagonist, less active enantiomer 10 mg 50 mg 1970 Potent, non-competitive NMDA antagonist 10 mg 50 mg 5018 PEAQX tetrasodium salt Potent NMDA receptor antagonist; NR2A selective 10 mg 2557 Non-competitive NMDA receptor antagonist 10 mg 50 mg 2530 PPDA Subtype-selective NR2C/NR2D antagonist 10 mg 50 mg 2274 PPPA Competitive NR2A antagonist 10 mg 50 mg 4801 QNZ 46 NR2C/NR2D-selective NMDA receptor non-competitive antagonist 10 mg 50 mg

www.tocris.com | 11 Tocris Product Listing Series

Category Cat. No. Product Name Description Unit Size 2005 Ro 04-5595 NR2B-selective NMDA antagonist 10 mg 50 mg 1594 Ro 25-6981 NR2B-selective NMDA antagonist 1 mg 10 mg 50 mg 3343 Ro 8-4304 NR2B-selective NMDA antagonist 10 mg 50 mg 1250 SDZ 220-581 Competitive NMDA antagonist 10 mg 50 mg 4154 TCN 201 Selective NR1/NR2A receptor antagonist 10 mg 50 mg 4163 TCN 213 NMDA antagonist; selective for NR2A over NR2B 10 mg 50 mg 4072 TCN 237 Highly potent and selective NR2B antagonist 10 mg 2782 TCS 46b Orally active, subtype-selective NR1A/NR2B antagonist 10 mg 50 mg 2892 Threo Ifenprodil NR2B-selective NMDA antagonist; also σ agonist 10 mg 50 mg 3322 ZD 9379 Brain penetrant NMDA antagonist; acts at glycine site 10 mg Other 4105 CIQ Potentiator of NMDA receptors containing NR2C/NR2D 10 mg 50 mg

0226 d- NMDA potentiator; acts at glycine site 1 g 2224 MNI-caged-NMDA Caged NMDA 10 mg 2213 N20C Non-competitive NMDA receptor open-channel blocker 10 mg 50 mg 5996 R-Norketamine NMDA ; metabolite of Ketamine (Cat. No. 3131) 10 mg 6112 S-Norketamine NMDA receptor modulator; metabolite of Ketamine (Cat. No. 3131) 10 mg 4230 NPEC-caged-d-AP5 Caged d-AP5 (Cat.No. 0106) 10 mg 50 mg 5376 sodium salt NMDA Potentiator 50 mg 0958 Modulator at polyamine site on NMDA receptors 100 mg Other Glutamate Agonists 0217 d- Endogenous, non-selective agonist; less active enantiomer 1 g 0218 l-Glutamic acid Endogenous, non-selective agonist 1 g

0391 Spaglumic acid Weak activator of NMDA receptors; also selective mGlu3 agonist 50 mg Antagonists 0102 d-AP4 Broad spectrum EAA antagonist 10 mg 50 mg

0101 dl-AP4 Broad spectrum EAA antagonist 100 mg

3699 dl-AP4 Sodium salt Broad spectrum EAA antagonist; sodium salt of DL-AP4 50 mg (Cat. No. 0101)

0341 l-AP6 Selective agonist of the ‘quis’ effect 10 mg 50 mg

2538 l-BMAA Neurotoxic 10 mg 0321 (RS)-4-Carboxyphenylglycine Broad spectrum EAA ligand 10 mg 50 mg 0310 (RS)-4-Carboxy-3-hydroxyphenylglycine Broad spectrum EAA ligand 10 mg 50 mg 0328 (R)-3-Carboxy-4-hydroxyphenylglycine Ionotropic glutamate receptor antagonist 10 mg 50 mg 1395 (R)-3,4-DCPG AMPA antagonist; weak NMDA antagonist 10 mg 50 mg 1394 (RS)-3,4-DCPG Potent systemically active anticonvulsant. Racemate of 10 mg (R)‑3,4,‑DCPG (Cat. No. 1395) 50 mg 0112 γDGG Broad spectrum glutamate receptor antagonist 50 mg 0223 Broad spectrum EAA antagonist 1 g 3694 Kynurenic acid sodium salt Sodium salt of kynurenic acid (Cat. No. 0223) 100 mg

12 | ion channels Ligand-gated Ion Channels – continued

Category Cat. No. Product Name Description Unit Size

Other 5785 MDNI-caged-l-glutamate Stable photoreleaser of l-glutamate 10 mg

1490 MNI-caged-l-glutamate Stable photoreleaser of l-glutamate 10 mg 50 mg

0395 N-Acetylglycyl-d-glutamic acid Potent convulsant 10 mg 50 mg 3574 RuBi-Glutamate Caged glutamate; excited by visible wavelengths 10 mg 0636 Salsolinol-1-carboxylic acid Endogenous amino acid 10 mg 50 mg 3847 Glutamate receptor ligand 50 mg Glycine Receptors Agonists 0206 β- Endogenous glycine agonist; more selective than 1 g (Cat. No. 0209) 0205 L-Alanine 1 g 0219 Glycine Endogenous glycine agonist; also modulates NMDA 1 g receptor‑mediated 0208 Hypotaurine Non-selective endogenous glycine receptor agonist 100 mg 0227 L-Serine Weak endogenous glycine receptor agonist 1 g 0209 Taurine Non-selective, endogenous glycine receptor partial agonist 1 g HCN Channels

Blockers 2202 Zatebradine Blocks hyperpolarization-activated current (If) 10 mg 50 mg

1000 ZD 7288 Inhibits pacemaker (If) current 10 mg 50 mg

IP3 Receptors

Antagonists 1224 2-APB IP3 receptor antagonist; also TRP 10 mg 50 mg 2+ 1280 (-)-Xestospongin C Reported inhibitor of IP3-dependent Ca release 10 μg Other 6210 ci-IP3/PM Caged triphosphate 10 μg Purinergic (P2X) Receptors Agonists 3245 ATP P2 agonist 50 mg 4080 ATPγS P2 agonist; ATP (Cat. No. 3245) analog 10 mg

3312 BzATP P2X7 agonist and P2X1/P2Y1 partial agonist; also photoaffinity label 1 mg for ATPase 3209 α,β-Methyleneadenosine 5’-triphosphate P2 agonist 10 mg 1062 2-Methylthioadenosine triphosphate P2 purinergic agonist 10 mg

Antagonists 2972 A 438079 Competitive P2X7 antagonist 10 mg 50 mg

3701 A 740003 Potent and selective P2X7 antagonist 10 mg 50 mg

4473 A 804598 Potent and selective P2X7 antagonist 10 mg 50 mg

4232 A 839977 Potent P2X7 antagonist 10 mg 50 mg

3323 AZ 10606120 Potent P2X7 receptor antagonist 10 mg 50 mg

3317 AZ 11645373 Potent and selective human P2X7 antagonist 10 mg 50 mg

3579 5-BDBD Potent P2X4 receptor antagonist 10 mg 50 mg

5545 BX 430 Selective P2X4 allosteric antagonist 10 mg 50 mg 0845 Selective P2X purinergic antagonist; also potent inhibitor of 1 g l-glutamate uptake into synaptic vesicles 0683 iso-PPADS P2X antagonist 10 mg 50 mg

5299 JNJ 47965567 Potent and selective P2X7 antagonist; brain penetrant 10 mg 50 mg

www.tocris.com | 13 Tocris Product Listing Series Ligand-gated Ion Channels – continued

Category Cat. No. Product Name Description Unit Size

1277 KN-62 Non-competitive P2X7 antagonist 1 mg

1240 NF 023 Selective, competitive P2X1 antagonist 10 mg 50 mg

2548 NF 110 Potent P2X3 antagonist 10 mg 50 mg

2450 NF 157 Selective P2Y11/P2X1 antagonist 10 mg 50 mg

1199 NF 279 Potent and selective P2X1 antagonist 10 mg 50 mg

1391 NF 449 Highly selective P2X1 antagonist 10 mg 50 mg 0625 PPADS P2 purinergic antagonist 10 mg 50 mg

1309 PPNDS Potent, selective P2X1 antagonist 10 mg 50 mg

2188 Ro 0437626 Selective P2X1 antagonist 1 mg 10 mg

4391 Ro 51 Potent P2X3, P2X2/3 antagonist 10 mg 50 mg

3052 RO-3 Selective P2X3 and P2X2/3 antagonist 10 mg

4386 TC-P 262 Selective P2X3, P2X2/3 antagonist 10 mg 50 mg 2464 TNP-ATP Potent, selective P2X antagonist 5 mg

Modulators 3385 GW 791343 P2X7 allosteric modulator 10 mg 50 mg Other 5157 DMNPE-caged ATP Caged ATP 10 mg

1203 MRS 2219 Potentiates P2X1-mediated responses 10 mg 50 mg

New Compound Libraries

Tocris has launched a range of new compound libraries composed of biologically active that have proven pharmacological activity against a wide range of targets. Use them in your phenotypic screening studies, drug repurposing campaigns or for validation of new molecular targets. Compounds are supplied pre-dissolved in DMSO, and full chemical and biological data are available. All compounds have the same proven , purity and stability as all those in the Tocris catalog.

Tocriscreen Plus (Cat. No. 5840) A unique library of 1280 biologically active compounds, including 177 ion channel modulators, with many exclusive to Tocris (250 mL 10 mM DMSO solutions). The collection is also available in smaller aliquots of 50 μL as the Tocriscreen Plus Mini (Cat No. 5841).

Tocriscreen Library of FDA Approved Compounds (Cat. No. 5932) A library of 160 FDA-approved compounds (250 mL 10 mM DMSO solutions)

Tocris also has a Custom Compound Library service available.

For more information visit www.tocris.com/tocriscreen

14 | ion channels Voltage-gated Ion Channels Voltage-gated ion channels are a group of transmembrane proteins that are activated by changes in membrane potential. The alteration in membrane potential induces a conformational change in the channel protein that either opens or closes the pore. Voltage-gated ion channels are important in excitable cells such as and myocytes, and they are classified according to ion selectivity, including Na+, K+, Ca2+. Also included in this group are a number of ion channel types that are relatively insensitive to changes in voltage, and are gated by second messengers or other intracellular or extracellular mediators, these include TRP channels and ryanodine receptors.

K Figure 2 | A representation of the voltage-gated ion ir KCNJ4 channel gene tree featuring genes of ion channels KCNJ6 KCNJ12 KCNJ11 targeted by Tocris products KCNJ5 KCNJ14 KCNJ2 KCNJ9 KCNJ8

KCNJ3

KCNJ1 KCNJ10 KCNJ16 K P KCNK3 2 KCNK10 KCNJ13 KCNJ15 KCNK5 KCNK13 KCNK2 KCNK12 CACNA1E KCNU1 CACNA1A CACNA1B Ca KCNK16 K V KCNK4 KCNK9 Ca KCNMA1 CACNA1G CACNA1C CACNA1H KCNK18 KCNK18 KCNN1 KCNN2 CACNA1S KCNK1 CACNA1I KCNN3 KCNN4 CACNA1D KCNK6 CACNA1F KCNK7 KCNK18 Na RYR3 V Kv9 SCN8A SCN4A SCN1A SCN9A SCN3A KCNS2 KCNS3 RYR2 SCN5A KCNS1 KCNG4 SCN10A K 6 RYR1 SCN2A v KCNG3 SCN11A KCNB2 KCNG2 Kv2 KCNB1 KCNG1 K 7 KCNQ5 v KCNQ4 TRPP3 KCNV1 KCNQ3 KCNV2 TRPP1 TRPP Kv8 KCNF1 KCNQ2 KCNC3 KCND3 KCNQ1 TRPP2 Kv5 KCNC4 KCND2 ITPR2 KCNA4 Kv4 IP KCNC1 KCNC2 KCND1 ITPR1 3 Kv3 ITPR3 KCNA10 KCNA3 Kv12 KCNA7 K 11 KCNA5 v KCNH6 KCNA2 KCNA1 KCNH4 TRPA1 KCNA6 KCNH2 KCNH8 TRPA TRPV3 K 1 KCNH3 v KCNH7 TRPV4 KCNH5 TRPV1 K 10 v KCNH1 TRPV2 TRPV HCN4 TRPV5 HCN3 ORAI3 MCOLN1 TRPV6 Gene Ion Channel ORAI2 abbreviation HCN2 MCOLN2 HCN1 TRPML CACNA calcium voltage-gated channel subunits (CaV) ORAI ORAI1 MCOLN3 HCN hyperpolarization-activated cyclic gated HCN TRPC2 ITPR IP receptor TRPC6 3 TRPC1 KCNA potassium voltage-gated channel subfamily A (Kv1) TRPC7 KCNB potassium voltage-gated channel subfamily B (Kv2) TRPM5 TRPC3 KCNC potassium voltage-gated channel subfamily C (K 3) TRPC4 TRPC v TRPM4 KCND potassium voltage-gated channel subfamily D (Kv4) TRPC5 KCNF potassium voltage-gated channel subfamily F (Kv5) KCNG potassium voltage-gated channel subfamily G (Kv6) TRPM8 KCNH potassium voltage-gated channel subfamily H TRPM1 (K 10, K 11 and K 12) TRPM2 v v v TRPM7 TRPM6 KCNJ potassium voltage-gated channel subfamily J (Kir) TRPM3 KCNK two-pore potassium channel family (K2P) KCNMA1 potassium calcium-activated channel subfamily TRPM

M alpha 1 (KCa1.1) KCNN potassium calcium-activated channel subfamily N

KCNQ potassium voltage-gated channel subfamily Q (Kv7) MCOLN transient receptor potential mucolipin family TRPC transient receptor potential canonical family KCNS potassium voltage-gated channel subfamily S (Kv9) ORAI ORAI calcium release-activated calcium modulators TRPM transient receptor potential melastatin family KCNU potassium calcium-activated channel subfamily U RYR TRPP transient receptor potential (polycystin)/polycystic

(KCa5.1) SCNA sodium voltage-gated channel alpha subunits (NaV) disease 2 family KCNV potassium voltage-gated channel subfamily V (Kv8) TRPA transient receptor potential ankyrin family TRPV transient receptor potential vanilloid family Adapted from www.guidetopharmacology.org

www.tocris.com | 15 Tocris Product Listing Series

Category Cat. No. Product Name Description Unit Size Calcium Channels Ryanodine Receptors

Activators 2793 Mobilizes calcium from intracellular stores; also A1 and A2B 100 mg antagonist and CNS 3905 NAADP RYR1 activator; Ca2+ mobilizing agent 10 mg 1472 hexasodium salt Increases RYR open probability; also non-selective P2 antagonist 100 mg Inhibitors 0507 Dantrolene Ryanodine receptor inhibitor; Ca2+ release inhibitor 100 mg 4564 JTV 519 Ryanodine receptor (RyR) inhibitor 10 mg 50 mg 1329 Ryanodine Ca2+ release inhibitor 1 mg STIM-Orai Channels Inhibitors 5490 5J 4 CRAC channel blocker; anti-inflammatory 10 mg 50 mg 0431 ML 9 STIM1-plasma membrane interaction inhibitor; also myosin light 10 mg chain inhibitor 50 mg 1866 MRS 1845 Potent SOCE inhibitor; blocks capacitative Ca2+ entry 10 mg 50 mg 1147 SKF 96365 Inhibits store-operated Ca2+ entry; also TRPC channel blocker 10 mg 50 mg 3939 YM 58483 Inhibitor of SOCE in non-excitable cells 10 mg 50 mg Voltage-gated Calcium Channels Activators 1544 (±)-Bay K 8644 Ca2+ channel activator (L-type) 10 mg 50 mg 1546 (S)-(-)-Bay K 8644 Ca2+ channel activator (L-type) 10 mg 50 mg 1403 FPL 64176 Potent activator of Ca2+ channels (L-type) 10 mg 50 mg

Ion Channels in Cancer Research Ion channels have recently emerged as playing a key role in the pathophysiology of cancer. Ion channels are present in all cancers and are involved in tumor development, proliferation, progression and invasiveness. For a comprehensive review of the role of ion channels in cancer see: Djamgoz et al. (2014) Philos.Trans.R.Soc.B.Biol.Sci. 369 (theme issue). Below is a selection of Tocris compounds that may be of use for exploring the role of ion channels in cancer.

O N H F3C Me N N S N N Me N NH S N O O

CF3 O

E 4031 (1808) YM 58483 (3939) 2+ K 11.1 (hERG) channel blocker Store-operated Ca entry (SOCE) blocker V in non-excitable cells; inhibits calcium release-activated calcium (CRAC) channels O O O O O O O O O O Thr-Ile-Ile-Asn-Val-Lys-Cys-Thr-Ser-Pro- O O N O O Lys-Gln-Cys-Leu-Pro-Pro-Cys-Lys-Ala-Gln- O N O O O Phe-Gly-Gln-Ser-Ala-Gly-Ala-Lys-Cys-Met-

Asn-Gly-Lys-Cys-Lys-Cys-Tyr-Pro-His

BAPTA AM (2787) (3563)

Blocks hK V1.5, hK V11.1 (hERG) Potent KV1.3 channel blocker

and hKV1.3 channels; also cell-permeable calcium chelator

16 |

Cancer feature products ion channels Voltage-gated Ion Channels – continued

Category Cat. No. Product Name Description Unit Size

Blockers 2799 ω- IVA Ca2+ channel blocker (P-type) 10 μg 2802 ω-Agatoxin TK Ca2+ channel blocker (P/Q-type) 10 μg 1085 ω-Conotoxin GVIA Ca2+ channel blocker (N-type) 250 μg 1084 ω-Conotoxin MVIIC Ca2+ channel blocker (N, P and Q-type) 100 μg 2004 Ca2+ channel blocker (L-type) 10 mg 50 mg 2198 Ca2+ channel blocker (T-type) 10 mg 50 mg 4507 ML 218 Ca2+ channel blocker (T-type) 10 mg 50 mg 5711 Ca2+ channel blocker (L-type); also Syk kinase inhibitor 50 mg 0600 Ca2+ channel blocker (L-type) 100 mg 2268 NNC 55-0396 Highly selective Ca2+ channel blocker (T-type) 10 mg

4665 ProTx I CaV3.1 channel blocker; also inhibits NaV1.8 and KV2.1 100 μg

2945 SNX 482 Potent and selective CaV2.3 blocker (R-type) 10 μg

Others 0806 Selectively binds the α2δ subunit of CaV channels. 10 mg 50 mg 3775 Selectively binds the α2δ subunit of voltage-sensitive calcium 10 mg channels; anticonvulsant 50 mg Other Calcium Channels Activators 5586 Yoda 1 Piezo1 channel activator 10 mg 50 mg 4741 Gadolinium chloride Stretch-activated blocker; calcium-sensing 50 mg receptor agonist Potassium Channels Ca2+-Activated Potassium Channels

Activators 2665 BMS 191011 Potent BKCa (KCa1.1) 10 mg 50 mg

2953 CyPPA Activator of KCa2.2 and KCa2.3 channels 10 mg 50 mg

1041 1-EBIO Activator of epithelial KCa channels 10 mg 50 mg

4311 GW 542573X Selective activator of KCa2.1 channels 10 mg 50 mg

4788 NS 11021 Activator of BKCa (KCa1.1) channels 10 mg 50 mg

3804 NS 1619 Activator of BKCa (KCa1.1) channels 10 mg

5276 NS 19504 Activator of BKCa (KCa1.1) channels 10 mg 50 mg

3895 NS 309 Positive modulator of KCa2 and KCa3.1 channels 10 mg 50 mg

3670 SKA 31 Activator of KCa3.1 and KCa2 channels 10 mg 50 mg

Blockers 1652 Apamin KCa2 channel blocker (small conductance) 1 mg

1087 KCa channel blocker (big conductance) 10 μg

1086 Iberiotoxin KCa channel blocker (big conductance) 100 μg

5571 Lei-Dab 7 High affinity, selective CK a2.2 blocker 100 μg

4864 NS 6180 Potent KCa3.1 channel blocker 10 mg 50 mg 2006 Potent BKCa channel blocker; also SERCA ATPase blocker. 10 mg

4617 Potent and selective BKCa (KCa1.1) channel blocker 1 mg

2946 TRAM 34 Potent and highly selective KCa3.1 channel blocker 10 mg 50 mg

4952 TRAM 39 Potent KCa3.1 blocker 10 mg 50 mg

www.tocris.com | 17 Tocris Product Listing Series

Category Cat. No. Product Name Description Unit Size

1310 UCL 1684 Highly potent blocker of KCa2 5 mg 2661 UCL 2077 Slow afterhyperpolarization (sAHP) channel blocker; sub-type 10 mg

selective Kv channel effects 50 mg

Modulators 4597 NS 8593 Selective KCa2 (SK) channel negative modulator; inhibits SK currents 10 mg 50 mg

Inward Rectifier Potassium (Kir) Channels

Activators 1377 Kir6 (KATP) channel opener 10 mg 50 mg

0964 Kir6 (KATP) channel opener; blocks desensitization of AMPA receptors 100 mg

1378 Levcromakalim Kir6 (KATP) channel opener; active enantiomer of cromakalim 10 mg (Cat. No. 1377) 50 mg

0583 Kir6 channel (KATP) opener 100 mg

5380 ML 297 Selective Kir3.1/3.2 (GIRK1/2) channel activator 10 mg 50 mg

2147 Kir6 (KATP) channel opener and NO donor 50 mg

1355 P1075 Potent Kir6 (KATP) channel opener 10 mg 50 mg

2580 Tenidap Opener of Kir2.3; also NSAID, cyclooxygenase (COX-1) inhibitor 10 mg 50 mg

2076 Y-26763 Kir6 (KATP) channel opener 10 mg 50 mg

2077 Y-27152 Prodrug of Kir6 (KATP) channel opener Y-26763 (Cat. No. 2076); 10 mg orally active in vivo 50 mg

0882 ZM 226600 Kir6 (KATP) channel opener 10 mg 50 mg

Blockers 3590 Gambogic acid Kir2.1 channel blocker; also activates caspases and inhibits Bcl-2 10 mg family proteins 50 mg

0911 Kir6 (KATP) channel blocker 100 mg

2396 Kir6 (KATP) channel blocker 10 mg 50 mg

4549 ML 133 Kir2 channel blocker 10 mg 50 mg

Venoms contain peptide that are injected by an animal, via biting or stinging, into its prey. A variety of animals produce venoms, including snakes, , cone snails, , bees and wasps. Many toxins act as blockers of ions channels and are of use in research because of their potency and high degree of selectivity for their target channel. A number of marketed medicines are based on derived from animal venoms, including the analgesic (Prialt), which originates from a cone snail and acts as a . Below is an example of an ion channel blocker, available from Tocris, which is the active ingredient of a venom.

Leu-Lys-Cys-Tyr-Gln-His-Gly-Lys-Val-Val-

Thr-Cys-His-Arg-Asp-Met-Lys-Phe-Cys-Tyr-

His-Asn-Thr-Gly-Met-Pro-Phe-Arg-Asn-Leu-

Lys-Leu-Ile-Leu-Gln-Gly-Cys-Ser-Ser-Ser-

Cys-Ser-Glu-Thr-Glu-Asn-Asn-Lys-Cys-Cys-

Ser-Thr-Asp-Arg-Cys-Asn-Lys

Mambalgin 1 (5938) Dendroaspis polylepsis, the Black , Selective ASIC1a inhibitor a source of Mambalgin 1

By Dick Culbert from Gibsons, B.C., Canada – Dendroaspis polylepis – the Black Mamba, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=50155545

18 |

Venoms feature products ion channels Voltage-gated Ion Channels – continued

Category Cat. No. Product Name Description Unit Size

4231 Kir6 (KATP) blocker; displays high affinity for SUR1/Kir6.2 channels 10 mg 50 mg

2095 PNU 37883 Vascular Kir6 (KATP) channel blocker 10 mg 50 mg

3805 Kir6 (KATP) channel blocker 50 mg

0925 SCH 23390 Kir3 channel blocker; standard selective D1-like antagonist; also 10 mg 5-HT2C and 5-HT1C agonist 50 mg

4339 LQ Selective Kir1.1 blocker; derivative of tertiapin-Q (Cat. No. 1316) 1 mg 1316 Tertiapin-Q Selective blocker of inward-rectifier +K channels 1 mg

3891 VU 590 Inhibitor of Kir1.1 (ROMK) and Kir7.1 10 mg 50 mg

4197 VU 591 Selective Kir1.1 (ROMK) inhibitor 10 mg 50 mg Two-P Potassium Channels

Activators 3797 BL 1249 Putative K2P2.1 (TREK-1) channel opener 10 mg 50 mg Blockers 5337 ML 365 Potent and selective TASK-1 channel blocker 10 mg 50 mg 5338 PK-THPP Potent TASK-3 channel blocker 10 mg 50 mg 5594 Spadin Potent TREK-1 channel blocker 1 mg

Voltage-gated Potassium (Kv) Channels

Activators 2867 KV7 channel activator 10 mg 50 mg

4519 ML 213 KV7.2 and KV7.4 channel opener 10 mg 50 mg

3062 NS 1643 KV11.1 (hERG) channel activator; antiarrhythmic 10 mg 50 mg

5083 QO 58 KV7 channel opener 10 mg 50 mg

Blockers 0940 4-Aminopyridine Non-selective KV channel blocker 100 mg

5659 AmmTX3 KV4 channel blocker 10 μg

3489 KV11.1 (hERG) channel blocker; also orally active, potent 50 mg

5929 BeKm 1 Potent and selective KV11.1 (hERG) channel blocker 100 μg

1808 E-4031 KV11.1 (hERG) channel blocker; inhibits rapid delayed rectifier 10 mg + K current (IKr) 50 mg

5676 1E Potent KV2.1 and KV2.2 channel blocker 100 μg

5011 HMR 1556 Potent and selective IKs channel blocker 10 mg

3899 JNJ 303 Potent and selective IKs blocker 10 mg 50 mg

3564 KV and KCa blocker 100 μg + 1278 KN 93 CaM kinase II inhibitor; also K channel blocker (KV) 1 mg

1999 KV7 (KCNQ) channel blocker 10 mg 50 mg

3563 Margatoxin Potent KV1.3 channel blocker 100 μg

2000 XE 991 Potent, selective KV7 (KCNQ) channel blocker; blocks M-currents 10 mg 50 mg

Others 2787 BAPTA AM Blocks hKV1.5, hKV11.1 (hERG) and hKV1.3 channels; also 25 mg cell-permeable Ca2+ chelator

5858 Exhibits affinity for hERG channels; also D2 receptor antagonist 50 mg Non-selective / Other Potassium Channels Blockers 4739 Cesium chloride Potassium channel blocker; neuroprotective 50 mg 2330 DMP 543 K+ channel blocker and potent ACh release enhancer 10 mg 50 mg Others 0416 YS-035 Inhibits K+ outward/ 10 mg 50 mg

www.tocris.com | 19 Tocris Product Listing Series

Category Cat. No. Product Name Description Unit Size Sodium Channels Voltage-gated Sodium Channels

Activators 5941 OD1 Potent hNav1.4, rNav1.6 and rNav1.7 channel activator 10 μg 2918 Veratridine Voltage-gated Na+ channel opener 10 mg 50 mg

Blockers 6159 4,9-Anhydrotetrodotoxin Potent and selective Nav1.6 channel blocker 100 μg 1470 acetate Cardiac Na+ channel blocker; antiarrhythmic 10 mg 50 mg

4718 IV Selective Nav1.7 channel blocker 100 μg

5066 ICA 121431 Potent and selective Nav1.3 and Nav1.1 channel blocker 10 mg 50 mg

5931 PF 05089771 Potent and selective Nav1.7 channel blocker 10 mg 50 mg

5792 ProTx III Potent Nav1.7 blocker; analgesic 100 μg 1014 QX 314 Na+ channel blocker 100 mg 2313 QX 314 chloride Na+ channel blocker 50 mg 0768 Blocks voltage-dependent Na+ channels; also glutamate release 25 mg inhibitor/GABA uptake inhibitor 1078 Na+ channel blocker 1 mg 1069 Tetrodotoxin citrate Na+ channel blocker; citrate salt of tetrodotoxin (Cat. No. 1078) 1 mg 2815 Valproic acid, sodium salt Blocks voltage-dependent Na+ channels; also histone deacetylase 100 mg inhibitor Transient Receptor Potential Channels TRPA1 Activators 5178 ASP 7663 Selective TRPA1 activator 10 mg 50 mg Blockers 2896 HC 030031 Selective TRPA1 blocker 10 mg 50 mg TRPC Activators 4522 Activates TRPC6; NSAID 50 mg

Blockers 5371 Clemizole TRPC5 blocker; also H1 antagonist 10 mg 50 mg 4912 GsMTx4 TRPC1 and TRPC6 blocker; inhibits mechanosensitive ion channels 100 μg 5807 M 084 TRPC4/5 channel blocker; antidepressant and anxiolytic 10 mg 50 mg 4732 ML 204 Selective TRPC4 blocker 10 mg 50 mg 3751 Pyr3 Selective TRPC3 blocker 10 mg 50 mg TRPM Activators 5521 CIM 0216 Selective TRPM3 agonist 10 mg 50 mg 1531 Activates a novel cold receptor. Cooling agent 10 mg 50 mg 3040 WS 12 TRPM8 agonist; cooling agent 10 mg 50 mg 2927 WS 3 TRPM8 agonist; cooling agent 10 mg 50 mg Blockers 3989 AMTB TRPM8 blocker 10 mg 50 mg 5324 M8 B Potent and selective TRPM8 channel blocker 10 mg 50 mg 5143 TRPM3 blocker 50 mg 6003 PF 0515679 Selective TRPM8 blocker 10 mg 4999 9-Phenanthrol Selective TRPM4 blocker 50 mg 5388 RQ 00203078 Potent and selective TRPM8 antagonist; orally active 10 mg 50 mg

20 | ion channels Voltage-gated Ion Channels – continued

Category Cat. No. Product Name Description Unit Size 5410 TC-I 2014 Potent TRPM8 antagonist 10 mg 50 mg 4632 TC-I 2000 TRPM8 blocker 10 mg 50 mg TRPML Activators 5547 MK6-83 TRPML channel activator 10 mg 50 mg 4746 ML SA1 Activator of TRPML channels 10 mg 50 mg 4907 SN 2 Selective TRPML3 channel activator 10 mg 50 mg TRPP Blockers 3378 EIPA Inhibits TRPP3-mediated currents; also inhibits the Na+/H+ 10 mg exchanger (NHE) 50 mg 3379 Phenamil Inhibits TRPP3-mediated currents; also inhibits epithelial Na+ 10 mg channels 50 mg TRPV Agonists 1116 AM 404 Vanilloid receptor agonist; also transport inhibitor 10 mg 50 mg 1339 Anandamide Endogenous TRPV1 and CB receptor agonist 5 mg 25 mg 1017 Anandamide (in Tocrisolve™ 100) Endogenous TRPV1 and CB receptor agonist 10 mg (in water-soluble emulsion) 50 mg 1354 Arvanil Potent TRPV1 and CB1 agonist; also anandamide transport inhibitor 5 mg 25 mg

Ion Channels in Research: A variety of ion channels are expressed by stem cells and have recently been shown to have a role in the regulation of self-renewal, differentiation and maturation of cells. Blockade or activation of ion channels may impact on the differentiation of stem cells towards certain lineages. Pharmacological reagents targeting ion channels can also be used to characterize differentiated cells. Research in this area is of interest in tissue repair, for example wound healing or neurodegenerative diseases, disease modeling, drug target discovery and testing. Below is a selection of compounds that may be of use in determining how specific channels function to direct the differentiation of stem cells.

O NO F3C O 2 O OMe MeO C CO Me O2N H 2 2 OMe N N Me N Me F Me N Me N Me H H

(±)-Bay K 8644 (1544) Mibefradil (2198) (1075) Potent L-type (voltage-gated) T and L-type (voltage-gated) Ca 2+ L-type (voltage-gated) Ca 2+ Ca2+ channel blocker channel blocker channel blocker

O

N O Cl N N N S S

N Cl N N N N Yoda 1 (5586) Linopirdine (1999) Piezo1 channel activator XE 991 (2000) Voltage-gated potassium channel blocker; Potent and selective voltage-gated potassium

blocks KV 7.1 + 7.3 (M-currents) and channel blocker. Blocks K V 7.2+7.3 (M-currents)

K V 7.1 (KCNQ1) homomeric channels and KV 7.1 homomeric channels

www.tocris.com | 21

Stem Cell feature products Tocris Product Listing Series

Category Cat. No. Product Name Description Unit Size 0462 (E)- Prototypic vanilloid receptor agonist 100 mg 1556 6ʹ-Iodoresiniferatoxin High affinity TRPV1 agonist/partial agonist 1 mg 1568 NADA Vanilloid agonist; also endogenous CB1 agonist and inhibitor of 5 mg FAAH and AMT 25 mg 1641 OLDA Potent, selective endogenous TRPV1 agonist 5 mg 25 mg 0934 Olvanil Potent vanilloid receptor agonist 10 mg 50 mg 1466 PPAHV Non-pungent vanilloid receptor agonist 1 mg 1137 Potent vanilloid receptor agonist 1 mg 3745 RN 1747 Selective TRPV4 agonist 10 mg 50 mg Antagonists 5781 A 425619 Potent TRPV1 antagonist 10 mg 50 mg 4319 A 784168 Potent and selective TRPV1 antagonist 10 mg 50 mg 4330 AMG 21629 Potent and selective TRPV1 antagonist 1 mg 5995 AMG 517 Potent TRPV1 antagonist 10 mg 50 mg 2316 AMG 9810 Potent and selective, competitive antagonist of TRPV1 10 mg 50 mg 2836 Arachidonyl serotonin Dual TRPV1 antagonist/FAAH inhibitor 10 mg 3875 BCTC TRPV1 antagonist 10 mg 50 mg 5106 GSK 2193874 Potent and selective TRPV4 antagonist; orally active 10 mg 50 mg 4100 HC 067047 Potent and selective TRPV4 antagonist 10 mg 50 mg 1975 6-Iodonordihydrocapsaicin Potent, competitive vanilloid receptor antagonist 10 mg 50 mg 3361 JNJ 17203212 Reversible, competitive and potent TRPV1 antagonist 10 mg 50 mg

1577 L-R4W2 TRPV1 antagonist peptide 1 mg 3746 RN 1734 Selective TRPV4 antagonist 10 mg 50 mg 5678 RN 9893 Potent and selective TRPV4 antagonist 10 mg 50 mg 1615 SB 366791 Potent, selective, competitive TRPV1 antagonist 10 mg 50 mg 3265 SB 452533 Potent TRPV1 receptor antagonist 10 mg 50 mg 4729 α-Spinasterol TRPV1 antagonist; active in vivo 1 mg Others 5246 MRS 1477 TRPV1 positive allosteric modulator 10 mg 50 mg 2203 PALDA Endogenous lipid; potentiates effects of endovanilloids at TRPV1 10 mg receptors 2204 STEARDA Endogenous lipid, active in vivo; enhances effects of endovanilloids 10 mg at TRPV1 receptors 1098 Tranilast Inhibits TRPV2-mediated responses; also inhibits inflammatory 10 mg mediator release from mast cells 50 mg

22 | ion channels

The Comprehensive in Vitro Proarrhythmia Assay (CiPA) Initiative: Prior to 2005, a number of medicines were withdrawn from the market following the finding that they delayed ventricular (prolongation of the QTc interval in the ECG) causing serious , known as Torsades de Pointes (TdP). This life-threatening effect was found to result from the ability of these drugs to block voltage-gated potassium channels (Kv11.1 or hERG). Among drugs withdrawn from the market owing to proarrhythmic effects were: the astemizole, the antibiotic grepafloxacin, and the treatment for gastroesophageal reflux, .

In 2005 new regulatory guidelines, E14 and ICH S7B, were introduced requiring all new Normal ECG Trace drugs to be tested for their effects on the QT interval in both clinical and preclinical tests. R These guidelines have proved effective in preventing the introduction of new medicines that T might cause TdP. However, Kv11.1 is only one of several ion channels controlling ventricular P Q S repolarization, but E14 and ICHS7B focus only on the effect of compounds on vK 11.1 channels, so there is a possibility that these guidelines may prevent the further development QT interval of useful drugs that induce QTc prolongation, but do not increase the risk of TdP. The Comprehensive in Vitro Proarrhythmia Assay (CiPA) initiative has been established to address this situation and aims to develop a new mechanism for assessing the proarrhythmia risk of drugs in development, with a view to revising current guidelines for approval of medicines. CiPA will have four main components: in vitro ion channel assays; computer modeling of cardiac ; confirmation of activity in stem cell-derived cardiomyocytes; and clinical assessment of electrophysiologic effects in phase I ECG studies. For the in vitro assays, voltage clamp protocols have been developed for key cardiac ion channels, including Kv11.1, Nav1.5, Cav1.2, Kv4.3, Kir2.1, KCNQ + KCNE, to test new drugs. In addition the CiPA steering group has generated a list of 28 drugs with known effects on cardiac electrophysiology, categorized as having high, intermediate or low risk of TdP. These drugs can be used for assay validation and calibration.

CiPA Compound Test Set

High Risk Intermediate Risk Low risk Azilimide Astemizole Loratadine Cisapride Metoprolol Nifedipine Vandetanib Droperidol D,L- Tamoxifen Risperidone Ondansetron

www.tocris.com | 23 Tocris Product Listing Series Other Channels This group includes compounds targeting chloride channels, aquaporins (channels that allow the passage of water), ionophores (ion carrying compounds), photoswitchable ligands and compounds that modulate multiple ion channels.

Category Cat. No. Product Name Description Unit Size Aquaporins Blockers 5412 TC AQP1 1 1 (AQP1) channel blocker 10 mg 50 mg 5425 TGN 020 Aquaporin 4 (AQP4) channel blocker 10 mg 50 mg Chloride Channels Calcium-activated Chloride Channels Activators 4876 Eact Activator of Ca2+-activated Cl– channel 16A 10 mg (TMEM16A) 50 mg Blockers 6076 Ani 9 Potent and selective TMEM16A (Anoctamin-1; ANO1) blocker 10 mg 50 mg 5420 TMEM16A/B calcium-activated (CaCC) blocker 50 mg 4877 CaCCinh-A01 Calcium-activated chloride channel (CaCC) inhibitor 10 mg 50 mg 5770 MONNA Potent TMEM16A (Anoctamin-1) blocker 10 mg 50 mg 0593 NPPB Inhibits calcium-sensitive chloride currents 50 mg 4538 T16Ainh - A01 Ca2+-activated Cl– channel transmembrane protein 16A (TMEM16A) 10 mg inhibitor 50 mg – – 2510 Talniflumate CaCC blocker and Cl /HCO3 exchange inhibitor 10 mg 50 mg CFTR - Activators 1422 DCEBIO Activates Cl conductance and hKCa3.1 channels 10 mg 50 mg

Blockers 3430 CFTRinh 172 Voltage-independent, selective CFTR 10 mg 50 mg 5485 GlyH 101 Reversible, voltage-dependent CFTR chloride channel blocker 10 mg 50 mg 1646 CFTR Cl- channel blocker; also mitochondrial hexokinase inhibitor 10 mg 50 mg 4303 PPQ 102 Potent, voltage-independent CFTR chloride channel inhibitor 10 mg 50 mg Others 3143 KM 11060 Corrects F508del-CFTR trafficking 10 mg 50 mg 3943 PG 01 CFTR mutants potentiator 10 mg 50 mg Other Chloride Channels

Blockers 1540 DCPIB Selective blocker of VSAC/ICl, swell; inhibits -stimulated 10 mg insulin release 50 mg 4523 DIDS CIC-Ka chloride channel blocker; TRPV1 modulator; RAD51 50 mg recombinase inhibitor 4911 GaTx2 High affinity, selective ClC-2 blocker; inhibits slow-gating 100 μg

Others 0963 9-AC Chloride transport inhibitor; also inhibits PKA activated cardiac ICl 100 mg Ionophores Others 1234 A23187, free acid Calcium ionophore 10 mg 1704 Ionomycin calcium salt Calcium ionophore 1 mg 2092 Ionomycin free acid Calcium ionophore 1 mg 5223 Monensin sodium salt Sodium ionophore; antibacterial agent 500 mg 4312 sodium salt Selective K+ ionophore 10 mg 2505 Nonactin Monovalent cation ionophore 10 mg 3373 Selective K+ ionophore 10 mg 50 mg

24 | ion channels

Category Cat. No. Product Name Description Unit Size Photoswitchable Ligands

Others 5462 AAQ chloride Photoswitchable Kv channel blocker 10 mg 50 mg 5464 AC 4 Photoswitchable TRPV1 channel blocker 10 mg 50 mg 5463 PA 1 Photoswitchable ENaC blocker 10 mg 50 mg

5470 QAQ dichloride Photoswitchable Nav, Kv and Cav channel blocker 10 mg 50 mg Other Channel Modulators Others 4095 Broad spectrum ion channel blocker; antiarrhythmic 50 mg 2090 CALP1 Cell-permeable agonist 1 mg 5449 Erastin Mitochondria VDAC modulator; also Ferroptosis activator 10 mg 2+ 3908 Ibutilide Blocks IKr, hERG and L-type Ca channels; class III antiarrhythmic 50 mg 1611 Blocks Na+, K+ and Ca2+ channels; also inhibits glutamate release. 10 mg Anticonvulsant 50 mg 2289 Lamotrigine isethionate Inhibits glutamate release. Water-soluble salt of lamotrigine 10 mg (Cat. No. 1611) 50 mg 2314 LOE 908 Broad spectrum cation channel blocker; neuroprotective 10 mg 50 mg 2851 Activates L/N-type calcium channels, cholinergic, 100 mg vand GABAergic systems; cognitive enhancer 3692 4,4-Pentamethylenepiperidine M2 channel blocker 50 mg 4108 Quinidine Blocks sodium and potassium channels 50 mg 2906 TRO 19622 Binds voltage-dependent anion channel (VDAC) 10 mg 50 mg 2625 Blocks voltage-sensitive Na+ and Ca2+ channels (T-type) 10 mg 50 mg

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• • Learning and Memory • Nicotinic ACh Receptors • Research • • Neuronal 5HT Receptors • Cardiovascular Research • • GABA Receptors • Peripheral Sensitization • P2X and P2Y Receptors

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www.tocris.com | 25 Tocris Product Listing Series

A Selection of Antibodies Targeting Ion Channels Available from Bio-Techne

Species Description Antibody Applications Ligand-gated Ion Channels Epithelial Sodium Channels AF2968 Prostasin/Prss8 Mouse Prostasin/Prss8 Affinity Purified Polyclonal Ab ELISA Capture (Matched Antibody Pair), WB AF4599 Human Prostasin/Prss8 Human Prostasin/Prss8 Affinity Purified Polyclonal Ab IHC, IP, Simple Western, WB MAB4599 Human Prostasin/Prss8 Human Prostasin/Prss8 MAb (Clone 530622) IHC, IP, WB GABA-A Receptors AF1188 Rat GABA-B R2 Rat GABA-B-R2 Affinity Purified Polyclonal Ab IHC, WB AF5590 Human GABA-A R beta 3 Human GABA-A-R beta 3 Affinity Purified Polyclonal Ab IHC, Simple Western, WB AF7000 Human/Mouse/Rat GABA-B R1 Human/Mouse/Rat GABA-B-R1 Affinity Purified Polyclonal Ab IHC, WB MAB7000 Rat GABA-B R1 Rat GABA-B-R1 MAb (Clone 751216) IHC PPS022 Human/Mouse/Rat/Bovine/ GABA-A R alpha 1 GABA-A-R alpha 1 C-Terminus Affinity Purified Polyclonal Ab WB Canine/Primate/Zebrafish PPS023 Mouse/Rat/Bovine GABA-A R alpha 1 Mouse/Rat GABA-A-R alpha 1 N-Terminus Affinity PurifiedA P b WB PPS024 Human/Mouse/Rat/Bovine/ GABA-A R alpha 2 Human/Mouse/Rat/Bovine GABA-A-R alpha 2 Polyclonal Ab WB Canine/Primate PPS025 Human/Mouse/Rat/Bovine/ GABA-A R alpha 4 GABA-A-R alpha 4 C-Terminus Affinity Purified Polyclonal Ab WB Canine/Primate/Zebrafish PPS027 Mouse/Rat GABA-A R alpha 5 Mouse/Rat GABA-A-R alpha 5 C-Terminus Affinity PurifiedA P b WB PPS030 Human/Mouse/Rat GABA-A R beta 1 GABA-A-R beta 1 C-Terminus Affinity Purified Polyclonal Ab WB PPS031 Human/Mouse/Rat/Bovine/ GABA-A R beta 2 GABA-A-R beta 2 C-Terminus Affinity Purified Polyclonal Ab WB Canine/Primate PPS072 Human/Mouse/Rat/Bovine/ GABA-A R gamma 2 Human/Mouse/Rat/Bovine GABA-A-R gamma 2 Polyclonal Ab WB Chicken/Primate/Zebrafish PPS073 Human/Mouse/Rat/Xenopus GABA-B R2 Phospho-GABA-B-R2 (S892) Affinity Purified Polyclonal Ab IF, WB PPS090 Human/Mouse/Rat/Bovine GABA-A R delta GABA-A-R delta N-Terminus Affinity PurifiedA P b IHC, IP, WB Ionotropic Glutamate Receptors AF4514 Human mGluR5 Human mGluR5 Affinity Purified Polyclonal Ab IHC, WB AF4668 Human mGluR3 Human mGluR3 Affinity Purified Polyclonal Ab IHC, WB AF4836 Human mGluR1 Human mGluR1 Affinity Purified Polyclonal Ab WB AF7387 Human mGluR4 Human mGluR4 Affinity PurifiedA P b CyTOF-ready, Flow Cytometry, IHC AF8138 Human HCN4 Human HCN4 Affinity Purified Polyclonal Ab ICC MAB4405 Human mGluR7 Human mGluR7 MAb (Clone 437310) CyTOF-ready, Flow Cytometry MAB4514 Human mGluR5 Human mGluR5 MAb (Clone 464818) CyTOF-ready, Intracellular Staining by Flow Cytometry, WB MAB45141 Human mGluR5 Human mGluR5 MAb (Clone 464823) IHC MAB4676 Human mGluR2 Human mGluR2 MAb (Clone 455310) CyTOF-ready, Intracellular Staining by Flow Cytometry, WB MAB4836 Human mGluR1 Human mGluR1 MAb (Clone 511622) IHC MAB5277 Human mGluR8 Human mGluR8 MAb (Clone 476410) IHC, WB MAB8138 Human HCN4 Human HCN4 MAb (Clone 880904) ICC PPS007 Human/Mouse/Rat/Canine/ GluR1 Phospho-GluR1 (S831) Affinity Purified Polyclonal Ab WB Chicken PPS008 Human/Mouse/Rat/Primate GluR1 Phospho-GluR1 (S845) Affinity Purified Polyclonal Ab WB PPS009 Rat Glycine R Rat Glycine R Affinity Purified Polyclonal Ab IHC, WB PPS011B Human/Mouse/Rat GRIN1/NMDAR1 Human/Mouse/Rat GRIN1/NMDAR1 MAb (Clone R1JHL) IP, WB PPS033 Human/Mouse/Rat GRIN2C/NMDAR2C Human/Mouse/Rat GRIN2C/NMDAR2C Affinity PurifiedA P b IP, WB

PPS051 Human/Mouse/Rat/Chicken/ GluR2/3 Human/Mouse/Rat GluR2/3 Affinity Purified Polyclonal Ab WB Zebrafish PPS080 Mouse/Rat GRIN1/NMDAR1 Mouse/Rat GRIN1/NMDAR1 Variant C1 Affinity PurifiedA P b IHC, WB PPS081 Mouse/Rat GRIN1/NMDAR1 Mouse/Rat GRIN1/NMDAR1 Variant C2 Affinity PurifiedA P b IHC, WB PPS082 Human/Mouse/Rat GRIN1/NMDAR1 GRIN1/NMDAR1 Variant C2’ Affinity Purified Polyclonal Ab IHC, WB PPS083 Mouse/Rat GRIN1/NMDAR1 Mouse/Rat GRIN1/NMDAR1 Variant N1 Affinity PurifiedA P b IHC, WB Voltage-gated Ion Channels Potassium Channels AF2360 Human DPP6 Human DPP6 Affinity Purified Polyclonal Ab CyTOF-ready, Flow Cytometry, IHC, IP, WB MAB2360 Human DPP6 Human DPP6 MAb (Clone 274308) CyTOF-ready, Flow Cytometry, IP MAB23601 Human DPP6 Human DPP6 Ectodomain MAb (Clone 274311) IP, WB MAB4100 Human DPP10 Human DPP10 MAb (Clone 453601) WB PPS015 Rat/Xenopus Potassium Channel Potassium Channel Kv2.2 Affinity PurifiedA P b IHC, WB Kv2.2 PPS016 Mouse/Rat Potassium Channel Phospho-Potassium Channel Kv3.1 (S503) Affinity PurifiedA P b IHC, WB Kv3.1 Other Channels CFTR MAB1660 Human CFTR Human CFTR R Domain MAb (Clone 13-1) IF, IHC, IP, WB MAB25031 Human CFTR Human CFTR C-Terminus MAb (Clone 24-1) IHC, IP, WB ICC, immunocytochemistry; IF, immunofluorescence; IHC, immunohistochemistry; IP, ; WB, Western Blot. Find out more at bio-techne.com

26 | ion channels

References

Category Authors Year Title Journal Vol Page

Pharmacology Clapham et al. 2003 International Union of . XLIII. Compendium Pharmacol.Rev. 55 591 of voltage-gated ion channels: transient receptor potential channels.

Goldstein et al. 2005 International Union of Pharmacology. LV. Nomenclature Pharmacol.Rev. 57 527 and molecular relationships of two-P potassium channels.

Gutman et al. 2005 International Union of Pharmacology. LIII. Nomenclature Pharmacol.Rev. 57 473 and molecular relationships of voltage-gated potassium channels.

Verkman and 2009 Chloride channels as drug targets. Nat.Rev.Drug.Discov. 8 153 Galietta

Kellenberger and 2014 International Union of Basic and Clinical Pharmacology 67 1 Schild Review. XCI. Structure, function, and pharmacology of acid-sensing channels (ASICs) and the epithelial Na+ channel.

Boscardin et al. 2016 International Union of Basic and Clinical Pharmacology Br.J.Pharmacol. 173 2671 Review. The function and regulation of acid-sensing channels (ASICs) and the epithelial Na+ channel (ENaC): IUPHAR review 19.

Ion Channels in Djamgoz et al. 2014 Theme Issue. Ion transport and cancer: from initiation Philos.Trans.R.Soc.B. 369 Cancer Research to metastasis. Biol.Sci.

Ion Channels in Feske et al. 2012 Ion channels and transporters in lymphocyte function Nat.Rev.Immunol. 12 532 Immunology and immunity. Research Feske et al. 2015 Ion channels in innate and adaptive immunity. Annu.Rev.Immunol. 33 291

Vig and Kinet 2009 in immune cells. Nat.Immunol. 10 21

Stebbing et al. 2015 The role of ion channels in microglial activation and Front.Immunol. 6 497 proliferation – a complex interplay between ligand-gated ion channels, K+ channels, and intracellular Ca2+.

Ion Channels in Pathak et al. 2014 Stretch-activated ion channel Piezo1 directs lineage Proc.Natl.Acad.Sci.U.S.A. 111 16148 Stem Cell Research choice in human neural stem cells.

Nguemo et al. 2013 The L-type Ca2+ channel blocker nifedipine represses PLoS One 8 e53407 mesodermal fate determination in murine embryonic stem cells.

Iannotti et al. 2009 Expression, localization, and pharmacological role of J.Pharmacol.Exp.Ther. 332 811

KV7 potassium channels in proliferation, differentiation, and survival after myotoxic insults.

Zhou et al. 2011 Potential role of KCNQ/M-channels in regulating neuronal Exp.Neurol. 229 471 differentiation in mouse hippocampal and embryonic stem cell-derived neuronal cultures.

Rodríguez-Gómez 2012 T-type Ca2+ channels in mouse embryonic stem cells: Am.J.Physiol.Cell Physiol. 302 C494 et al. modulation during cell cycle and contribution to self‑renewal.

Ge et al. 2013 Distal C terminus of CaV1.2 channels plays a crucial role PLoS One 8 e81332 in the neural differentiation of dental pulp stem cells.

CiPA Colatsky et al. 2016 The comprehensive in vitro proarrhythmia assay (CiPA) J.Pharmacol.Toxicol. 81 233 initiative – update on progress. Methods

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