Regulation of intrinsic excitability in hippocampal neurons by activity-dependent modulation of the KV2.1 potassium channel

Channels (Austin). Jan-Feb 2009;3(1):46-56. doi: 10.4161/chan.3.1.7655.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Calcineurin / metabolism
  • Calcium / metabolism
  • Cells, Cultured
  • Computer Simulation
  • Glutamic Acid / metabolism*
  • Hippocampus / drug effects
  • Hippocampus / embryology
  • Hippocampus / metabolism*
  • Humans
  • Ion Channel Gating*
  • Kinetics
  • Models, Neurological
  • Neurons / drug effects
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Peptides / pharmacology
  • Phosphorylation
  • Potassium Channel Blockers / pharmacology
  • Rats
  • Shab Potassium Channels / antagonists & inhibitors
  • Shab Potassium Channels / genetics
  • Shab Potassium Channels / metabolism*
  • Transfection

Substances

  • Kcnb1 protein, rat
  • Peptides
  • Potassium Channel Blockers
  • Shab Potassium Channels
  • hanatoxin
  • dendrotoxin K
  • Glutamic Acid
  • Calcineurin
  • Calcium