Regulation of intrinsic excitability in hippocampal neurons  by activity-dependent modulation of the KV2.1 potassium channel.
KV2.1 is the prominent somatodendritic sustained or delayed rectifier voltage-gated potassium (KV) channel in mammalian central neurons, and is a target for activity-dependent modulation via calcineurin-dependent dephosphorylation. Using hanatoxin-mediated block of KV2.1 we show that, in cultured rat hippocampal neurons, glutamate stimulation leads to significant hyperpolarizing shifts in the voltage-dependent activation and inactivation gating properties of the KV2.1-component of delayed rectifier K+ (IK) currents. In computer models of hippocampal neurons, these glutamate- stimulated shifts in the gating of the KV2.1-component of IK lead to a dramatic suppression of action potential firing frequency. Current-clamp experiments in cultured rat hippocampal neurons showed glutamate stimulation induced a similar suppression of neuronal firing frequency. Membrane depolarization also resulted in similar hyperpolarizing shifts in the voltage-dependent gating properties of neuronal IK currents, and suppression of neuronal firing. The glutamate-induced effects on neuronal firing were eliminated by hanatoxin, but not by dendrotoxin-K, a blocker of KV1.1-containing channels. These studies together demonstrate a specific contribution of modulation of KV2.1 channels in the activity-dependent regulation of intrinsic neuronal excitability.
Mohapatra
Durga P
DP
Department of Neurobiology, Physiology and Behavior, College of Biological Sciences, University of California, Davis, CA 95616-8519, USA.
Misonou
Hiroaki
H
Pan
Sheng-Jun
SJ
Held
Joshua E
JE
Surmeier
D James
DJ
Trimmer
James S
JS
D000200:Action Potentials; D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003198:Computer Simulation; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating; D007700:Kinetics; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D051669:Shab Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
C496991:Kcnb1 protein, rat; D010455:Peptides; D026902:Potassium Channel Blockers; D051669:Shab Potassium Channels; C096469:hanatoxin; C081506:dendrotoxin K; D018698:Glutamic Acid; D019703:Calcineurin; D002118:Calcium