Ion Channels Product Listing | Edition 1
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Ion 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 proteins present in the plasma membrane of most cells, as well as the intracellular membranes surrounding many organelles, allowing the passage of ions across the membrane. They are essential for maintaining resting membrane potential, generating action potentials and other electrical signaling, and regulating cell volume. Ion channels have a fundamental role in physiological processes such as T cell activation, muscle contraction, insulin 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 Potassium Channels 17 Ca2+-Activated Potassium Channels 17 5-HT3 4 Inward Rectifier Potassium (K ) Channels 18 Acetylcholine 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 Receptor 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 Glycine Receptors 13 Other Channels 24 HCN Channels 13 Aquaporins 24 IP3 Receptors 13 Chloride Channels 24 Purinergic (P2X) Receptors 13 Calcium-activated Chloride Channels 24 CFTR 24 Voltage-gated Ion Channels 15 Other Chloride Channels 24 Calcium Channels 16 Ionophores 24 Ryanodine 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 ion channel gene tree featuring genes 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 cholinergic 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 glycine receptor alpha GABRA1 GLRB glycine receptor beta GABRA3 GABRA5 HTR3 5-hydroxytryptamine receptor 3 P2RX purinergic receptor P2X SCNN sodium channel 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 agonist 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 partial agonist 10 mg 50 mg 3547 Serotonin 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 Dihydroergotamine 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 Mirtazapine 5-hT3, 5-hT2, h1 and α2-antagonist; antidepressant 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 receptor antagonist 10 mg 50 mg 0641 Tropanyl-3,5-dimethylbenzoate 5-hT3 antagonist 100 mg 2459 Tropisetron 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 Agonists 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 neurotransmitter 50 mg 3964 aR-R 17779 α7-selective agonist 10 mg 2241 DMaB-anabaseine 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 cytokine release as well as O Th17 differentiation. influx; also TRPC channel inhibitor HN Calcium is a second messenger in O lymphocytes, regulating proliferation, gene expression, motility and other functions. STIM1 is the putative Ca2+ sensor on the HN SO3Na endoplasmic reticulum (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. channel blocker 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 antigen 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; histamine 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-Bungarotoxin α7 subtype-selective nachR antagonist 1 mg 3119 α-conotoxin ImI α7 and α9 selective nachR antagonist 500 μg 3405 coG 133 nicotinic α7 antagonist; apoe peptide fragment 1 mg 1029 Methyllycaconitine α7 neuronal nicotinic receptor antagonist 5 mg 25 mg 1356 MG