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

doi:10.4161/chan.3.1.7655

Regulation of intrinsic excitability in hippocampal neurons by activity-dependent modulation of the K_V2.1 potassium channel

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

Neuroscience

Research output: Contribution to journal › Article › peer-review

87 Scopus citations

Abstract

K_V2.1 is the prominent somatodendritic sustained or delayed rectifier voltage-gated potassium (K_V) channel in mammalian central neurons, and is a target for activity-dependent modulation via calcineurin-dependent dephosphorylation. Using hanatoxin-mediated block of K_V2.1 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 K_V2.1-component of delayed rectifier K⁺ (I_K) currents. In computer models of hippocampal neurons, these glutamate-stimulated shifts in the gating of the K_V2.1-component of I_K 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 I_K 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 K_V1.1-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 (US)
Pages (from-to)	46-56
Number of pages	11
Journal	Channels
Volume	3
Issue number	1
DOIs	https://doi.org/10.4161/chan.3.1.7655
State	Published - 2009

Funding

This work was supported by NIH/NINDS grants NS42225 (to James S. Trimmer) and NS34696 (to D. James Surmeier). Durga P. Mohapatra was supported in part by a postdoctoral fellowship grant from the Epilepsy Foundation through the generous support of the American Epilepsy Society and the Milken Family Foundation. We thank Dr. Kenton J. Swartz, for the generous gift of hanatoxin; Dr. Elva Diaz and Ms. Evgenia Kalashnikova for providing some of the cultured rat hippocampal neurons; Dr. Phillip A. Schwartzkroin for critical reading and constructive suggestions on the manuscript.

Keywords

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

ASJC Scopus subject areas

Biophysics
Biochemistry

Access to Document

10.4161/chan.3.1.7655

Cite this

@article{6a4daf1bcd204e01aad881a518e80737,

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

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.",

keywords = "Calcineurin, Hanatoxin, Hippocampal neuron, Homeostatic plasticity, Neuronal excitability, Phosphorylation, Voltage-gated potassium channel",

author = "Mohapatra, \{Durga P.\} and Hiroaki Misonou and Pan, \{Sheng Jun\} and Held, \{Joshua E.\} and Surmeier, \{D. James\} and Trimmer, \{James S.\}",

note = "Funding Information: This work was supported by NIH/NINDS grants NS42225 (to James S. Trimmer) and NS34696 (to D. James Surmeier). Durga P. Mohapatra was supported in part by a postdoctoral fellowship grant from the Epilepsy Foundation through the generous support of the American Epilepsy Society and the Milken Family Foundation. We thank Dr. Kenton J. Swartz, for the generous gift of hanatoxin; Dr. Elva Diaz and Ms. Evgenia Kalashnikova for providing some of the cultured rat hippocampal neurons; Dr. Phillip A. Schwartzkroin for critical reading and constructive suggestions on the manuscript.",

year = "2009",

doi = "10.4161/chan.3.1.7655",

language = "English (US)",

volume = "3",

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T1 - Regulation of intrinsic excitability in hippocampal neurons by activity-dependent modulation of the KV2.1 potassium channel

AU - Mohapatra, Durga P.

AU - Misonou, Hiroaki

AU - Pan, Sheng Jun

AU - Held, Joshua E.

AU - Surmeier, D. James

AU - Trimmer, James S.

N1 - Funding Information: This work was supported by NIH/NINDS grants NS42225 (to James S. Trimmer) and NS34696 (to D. James Surmeier). Durga P. Mohapatra was supported in part by a postdoctoral fellowship grant from the Epilepsy Foundation through the generous support of the American Epilepsy Society and the Milken Family Foundation. We thank Dr. Kenton J. Swartz, for the generous gift of hanatoxin; Dr. Elva Diaz and Ms. Evgenia Kalashnikova for providing some of the cultured rat hippocampal neurons; Dr. Phillip A. Schwartzkroin for critical reading and constructive suggestions on the manuscript.

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - Calcineurin

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KW - Hippocampal neuron

KW - Homeostatic plasticity

KW - Neuronal excitability

KW - Phosphorylation

KW - Voltage-gated potassium channel

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