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Research Paper
Regulation of intrinsic excitability in hippocampal neurons by activity-dependent modulation of the KV2.1 potassium channel
Durga P. Mohapatra, Hiroaki Misonou, Pan Sheng-Jun, Joshua E. Held, D. James Surmeier and James S. Trimmer
Volume 3, Issue 1January/February 2009
Pages 46 - 56
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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.
Authors
- Durga P. Mohapatra
- University of Iowa Carver College of Medicine
- Hiroaki Misonou
- University of California, Davis
- Pan Sheng-Jun
- University of California, Davis
- Joshua E. Held
- Northwestern University Feinberg School of Medicine
- D. James Surmeier
- Northwestern University Feinberg School of Medicine
- James S. Trimmer Corresponding author: jtrimmer@ucdavis.edu
- University of California, Davis
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
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