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 language | English |
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Pages (from-to) | 46-56 |
Number of pages | 11 |
Journal | Channels |
Volume | 3 |
Issue number | 1 |
DOIs | |
State | Published - 2009 |
Keywords
- Calcineurin
- Hanatoxin
- Hippocampal neuron
- Homeostatic plasticity
- Neuronal excitability
- Phosphorylation
- Voltage-gated potassium channel