title: M-channels (Kv7/KCNQ channels) that regulate synaptic integration, excitability, and spike pattern of CA1 pyramidal cells are located in the perisomatic region.
abstract: To understand how electrical signal processing in cortical pyramidal neurons is executed by ion channels, it is essential to know their subcellular distribution. M-channels (encoded by Kv7.2-Kv7.5/KCNQ2-KCNQ5 genes) have multiple important functions in neurons, including control of excitability, spike afterpotentials, adaptation, and theta resonance. Nevertheless, the subcellular distribution of these channels has remained elusive. To determine the M-channel distribution within CA1 pyramidal neurons, we combined whole-cell patch-clamp recording from the soma and apical dendrite with focal drug application, in rat hippocampal slices. Both a M-channel opener (retigabine [N-(2-amino-4-(4-fluorobenzylamino)-phenyl) carbamic acid ethyl ester]) and a blocker (XE991 [10,10-bis(4-pyridinylmethyl)-9(10H)-antracenone]) changed the somatic subthreshold voltage response but had no observable effect on local dendritic responses. Under conditions promoting dendritic Ca2+ spikes, local somatic but not dendritic application of M-channel blockers (linopirdine and XE991) enhanced the Ca2+ spikes. Simultaneous dendritic and somatic whole-cell recordings showed that the medium afterhyperpolarization after a burst of spikes underwent strong attenuation along the apical dendrite and was fully blocked by somatic XE991 application. Finally, by combining patch-clamp and extracellular recordings with computer simulations, we found that perisomatic M-channels reduce the summation of EPSPs. We conclude that functional M-channels appear to be concentrated in the perisomatic region of CA1 pyramidal neurons, with no detectable M-channel activity in the distal apical dendrites.
authors.affiliation: Department of Physiology at Institute of Basal Medicine and Centre of Molecular Biology and Neuroscience, University of Oslo, PB 1103 Blindern, N-0317 Oslo, Norway.
authors.forename: Hua
authors.initials: H
authors.lastname: Hu
authors.forename: Koen
authors.initials: K
authors.lastname: Vervaeke
authors.forename: Johan F
authors.initials: JF
authors.lastname: Storm
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002219:Carbamates / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D003198:Computer Simulation; D003712:Dendrites / Q000378:metabolism / Q000502:physiology; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D051656:KCNQ Potassium Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008959:Models, Neurological; D018408:Patch-Clamp Techniques; D010655:Phenylenediamines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017966:Pyramidal Cells / Q000378:metabolism* / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology*; D014018:Tissue Distribution
chemical_list: C112297:10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; D000873:Anthracenes; D002219:Carbamates; D007211:Indoles; D051656:KCNQ Potassium Channels; D010655:Phenylenediamines; D026902:Potassium Channel Blockers; D011725:Pyridines; C101866:ezogabine; C061017:linopirdine; D002118:Calcium