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AHP, BK- and SK-Channel References

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AHP, BK- and SK-Channel References AHP, BK- and SK-channel references This is an ongoing project (open-ended), so look at it only (ONLY!) as the first couple of hundred pages of a summary of what’s known about afterhyperpolarizations, the channels that gate them, and the pharmacology that effects them. Where abstracts are not listed, I couldn’t get ‘em. Posted 6/14/02. -Tres Thompson, Ph.D., Neuroscience HIPPOCAMPAL PYRAMIDAL NEURONS •Alberi, S., Boeijinga, P.H., Raggenbass, M. & Boddeke, H.W. (2000). Involvement of calmodulin-dependent protein kinase II in carbachol-induced rhythmic activity in the hippocampus of the rat. Brain Research 872(1-2): 11-19. The role of calcium and protein kinases in rhythmic activity induced by muscarinic receptor activation in the CA1 area in rat hippocampal slices was investigated. Extracellular recording showed that carbachol (20 µM) induced synchronized field potential activity with a dominant frequency of 7.39±0.68 Hz. Pretreatment with the membrane permeable Ca(2+) chelator BAPTA-AM (50 µM) or with thapsigargin (1 µM), a compound which depletes intracellular calcium stores, reduced the dominant power of carbachol-induced theta-like activity by 83% and 78%, respectively. Inhibition of calmodulin-dependent protein kinase II (CaMKII) by the cell permeable inhibitor KN-93 (10 µM) reduced the power of carbachol-induced theta-like activity by 80%. In contrast the protein kinase C (PKC) inhibitor calphostin C did not significantly (P>0.05) affect the effect of carbachol. Whole- cell recording indicated that KN-93 also blocked carbachol-induced suppression of slow I(AHP) and strongly inhibited the carbachol-induced plateau potential. Our data suggest that activation of CaMKII by carbachol is crucial for local theta-like activity in the CA1 area of the rat hippocampus in vitro. Furthermore, involvement of CaMKII in carbachol-induced suppression of the slow I(AHP) and the induction of plateau potentials could play a role in the induction of theta-like rhythmic activity by carbachol. •Andreasen, M. (2002). Inhibition of slow Ca2+-activated K+ current by 4- aminopyridine in rat hippocampal CA1 neurons. British Journal of Pharmacology 135(4): 1013-1025. The effect of 4-aminopyridine (4-AP) on the slow afterhyperpolarization (sAHP) seen after high frequency dendritic or somatic firing was investigated in rat Page 1 AHP, BK- and SK-channel references hippocampal CA1 pyramidal neurones (PC). Intracellular recordings were obtained from the distal apical dendrites and somata and suprathreshold depolarizing current pulses were used to evoke a sAHP. The sAHP was blocked by low concentrations of carbacholine (Cch) but insensitive to high concentrations of apamin. In the presence of extracellular 4-AP, the first dendritic sAHP evoked was reduced compared to a maximal sAHP evoked in the absence of 4-AP. The reduction was evident at submillimolar concentration and increased to about 80% with 4 mM 4-AP. The stability of the 4-AP-induced block was affected by the type of anion used in the electrode solution. With K(+) acetate (KAc) or K(+) methylsulphate (KMeSO(4)) containing electrodes, the block was progressively removed during the initial 300 - 400 s of recordings. With KCl containing electrodes, the block remained stable and was 10% larger than that obtained with acetate. Detailed investigations showed that intracellular acetate promotes the removal of the 4-AP-induced block in an activity-dependent manner. Intracellularly applied 4-AP also induced an acetate- sensitive block of the dendritic sAHP. 4-AP also blocked the somatic sAHP and the stability of the block showed the same sensitivity towards anions as the dendritic sAHP. Thus 4-AP appears to block the slow Ca2+-activated K(+) current underlying the sAHP in a complex manner which is sensitive to certain types of anions. •Andreasen, M. & Lambert, J.D.C. (2001). 4-aminopyridine inhibits a slow calcium-activated K+ current in hippocampal CA1 neurons. Society for Neuroscience Abstracts 31(382.17): 196. 4-aminopyridine (4-AP) blocks several types of voltage-gated K+ currents, but is generally reported to have no effect on Ca2+-activated K+ currents. Here we report that 4-AP blocks the slow afterhyperpolarization (sAHP) observed in the apical dendrites following high frequency firing and/or Ca2+ spikes. Sharp microelectrodes were used to obtain intracellular recordings from the distal apical dendrites of hippocampal CA1 pyramidal neurones in slices from adult male Wistar rats. Suprathreshold current pulses (300 ms, 0.1 Hz), were used to evoke the sAHP. With K+ acetate (KAc) containing electrodes, the size of the first sAHP evoked in the presence of 4-AP was much smaller than expected considering the concurrent increase in Ca2+ spiking. Compared to maximal sAHPs evoked in the absence of 4-AP, the sAHPs in the presence of 4-AP was reduced by 20 % in 250 M and by 80 % in 4 mM 4-AP. The reduction was maximal on the first stimulation. Thereafter, there was a progressive increase in the sAHP until a plateau was reached after 300 - 400 s despite the continued presence of 4-AP. The rate of unblocking of 4-AP was partly Page 2 AHP, BK- and SK-channel references dependent on the stimulation frequency. With KCl-containing electrodes, the reduction of the sAHP in the presence of 4-AP (4 mM) was 10 % larger than with KAc electrodes and, furthermore, remained stable for the whole of the recording period. Thus, 4-AP seems to block the slow Ca2+-activated K+ channels mediating the sAHP by binding to a site that is accessible when the channels are closed. Moreover, intracellular acetate somehow decreases the binding of 4-AP to the channel complex. •Bacon, W.L. & Beck, S.G. (2000). 5-Hydroxytryptamine7 receptor activation decreases slow afterhyperpolarization amplitude in CA3 hippocampal pyramidal cells. Journal of Pharmacology and Experimental Therapeutics 294(2): 672-679. The 5-hydroxytryptamine(7) (5-HT(7)) receptor was originally defined by molecular biology techniques. The 5-HT(7) receptor protein and mRNA are found in brain areas, such as the CA3 subfield of the hippocampus, that are involved in various neuropsychiatric disease states. No functional response has previously been attributed to activation of the 5-HT(7) receptor in any of these brain areas. Calcium spike-induced slow afterhyperpolarizations (sAHP) were recorded from CA3 hippocampal pyramidal cells using intracellular recording techniques in a brain slice preparation maintained in vitro. A concentration-dependent inhibition of the sAHP amplitude was obtained when 5-HT was used as the agonist. To identify whether the 5-HT(7) receptor was one of the receptors mediating the inhibition of the sAHP amplitude, 5-HT agonists and antagonists were tested in the presence of WAY- 100635 and GR-113808 to block 5-HT(1A) and 5-HT(4) receptor activation, respectively. The rank order potency of the agonists was 5-carboxyamidotryptamine (5-CT) > 5-HT > 5-methoxytryptamine (5-MeOT). Other agonists with high affinity at 5-HT(2), 5-HT(3), 5-HT(1B), 5-HT(1D), or 5-HT(6) receptors did not produce any response when tested at 10 microM. Ritanserin, mesulergine, and SB-269770 were competitive antagonists of the 5-CT inhibition of sAHP amplitude, with affinity (pA(2)) values of 6.8, 7. 9, and 8.8, respectively. Methiothepin was also an effective antagonist but was insurmountable. Other antagonists with affinity for the 5- HT(2), 5-HT(3), or 5-HT(6) receptor had no effect. Based on the rank order potency of the agonists and antagonists, one of the receptors that mediates the decrease in sAHP amplitude in CA3 hippocampal pyramidal cells was concluded to be the 5-HT(7) receptor. •Bekkers, J.M. (2000). Distribution of slow AHP channels on hippocampal CA1 pyramidal neurons. Journal of Neurophysiology 83(4): 2040-2046. Page 3 AHP, BK- and SK-channel references This work was designed to localize the Ca(2+)-activated K(+) channels underlying the slow afterhyperpolarization (sAHP) in hippocampal CA1 pyramidal cells. Cell-attached patches on the proximal 100 µm of the apical dendrite contained K(+) channels, but not sAHP channels, activated by backpropagating action potentials. Amputation of the apical dendrite approximately 30 µm from the soma, while simultaneously recording the sAHP whole cell current at the soma, depressed the sAHP amplitude by only approximately 30% compared with control. Somatic cell- attached and nucleated patches did not contain sAHP current. Amputation of the axon ≥20 microm from the soma had little effect on the amplitude of the sAHP recorded in cortical pyramidal cells. By this process of elimination, it is suggested that sAHP channels may be concentrated in the basal dendrites of CA1 pyramids. •Bond, C.T., Maylie, J. & Adelman, J.P. (1999). Small-conductance calcium- activated potassium channels. Annals of the NY Academy of Science 868: 370-8. SK channels play a fundamental role in all excitable cells. SK channels are potassium selective and are activated by an increase in the level of intracellular calcium, such as occurs during an action potential. Their activation causes membrane hyperpolarization, which inhibits cell firing and limits the firing frequency of repetitive action potentials. The intracellular calcium increase evoked by action potential firing decays slowly, allowing SK channel activation to generate a long- lasting hyperpolarization termed the slow afterhyperpolarization (sAHP). This spike-frequency adaptation protects the cell from the deleterious effects of continuous tetanic activity and is essential for normal neurotransmission. Slow AHPs can be classified into two groups, based on sensitivity to the bee venom toxin apamin. In general, apamin- sensitive sAHPs activate rapidly following a single action potential and decay with a time constant of approximately 150 ms. In contrast, apamin-insensitive sAHPs rise slowly and decay with a time constant of approximately 1.5 s.
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