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

Durga P. Mohapatra, Hiroaki Misonou, Sheng Jun Pan, Joshua E. Held, D. James Surmeier, James S. Trimmer

Research output: Contribution to journalArticle

62 Scopus citations

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 K V2.1 channels in the activity-dependent regulation of intrinsic neuronal excitability.

Original languageEnglish
Pages (from-to)46-56
Number of pages11
JournalChannels
Volume3
Issue number1
DOIs
StatePublished - Jan 1 2009

Keywords

  • Calcineurin
  • Hanatoxin
  • Hippocampal neuron
  • Homeostatic plasticity
  • Neuronal excitability
  • Phosphorylation
  • Voltage-gated potassium channel

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    Mohapatra, D. P., Misonou, H., Pan, S. J., Held, J. E., Surmeier, D. J., & Trimmer, J. S. (2009). Regulation of intrinsic excitability in hippocampal neurons by activity-dependent modulation of the KV2.1 potassium channel. Channels, 3(1), 46-56. https://doi.org/10.4161/chan.3.1.7655