Regulation of ion channel localization and phosphorylation by neuronal activity

Hiroaki Misonou; Durga P. Mohapatra; Eunice W. Park; Victor Leung; Dongkai Zhen; Kaori Misonou; Anne E. Anderson; James S. Trimmer

doi:10.1038/nn1260

Regulation of ion channel localization and phosphorylation by neuronal activity

Hiroaki Misonou, Durga P. Mohapatra, Eunice W. Park, Victor Leung, Dongkai Zhen, Kaori Misonou, Anne E. Anderson, James S. Trimmer

Washington University Pain Center

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

378 Scopus citations

Abstract

Voltage-dependent Kv2.1 K⁺ channels, which mediate delayed rectifier Kv currents (I_K), are expressed in large clusters on the somata and dendrites of principal pyramidal neurons, where they regulate neuronal excitability. Here we report activity-dependent changes in the localization and biophysical properties of Kv2.1. In the kainate model of continuous seizures in rat, we find a loss of Kv2.1 clustering in pyramidal neurons in vivo. Biochemical analysis of Kv2.1 in the brains of these rats shows a marked dephosphorylation of Kv2.1. In cultured rat hippocampal pyramidal neurons, glutamate stimulation rapidly causes dephosphorylation of Kv2.1, translocation of Kv2.1 from clusters to a more uniform localization, and a shift in the voltage-dependent activation of I_K. An influx of Ca ²⁺ leading to calcineurin activation is both necessary and sufficient for these effects. Our finding that neuronal activity modifies the phosphorylation state, localization and function of Kv2.1 suggests an important link between excitatory neurotransmission and the intrinsic excitability of pyramidal neurons.

Original language	English
Pages (from-to)	711-718
Number of pages	8
Journal	Nature neuroscience
Volume	7
Issue number	7
DOIs	https://doi.org/10.1038/nn1260
State	Published - Jul 2004

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title = "Regulation of ion channel localization and phosphorylation by neuronal activity",

abstract = "Voltage-dependent Kv2.1 K+ channels, which mediate delayed rectifier Kv currents (IK), are expressed in large clusters on the somata and dendrites of principal pyramidal neurons, where they regulate neuronal excitability. Here we report activity-dependent changes in the localization and biophysical properties of Kv2.1. In the kainate model of continuous seizures in rat, we find a loss of Kv2.1 clustering in pyramidal neurons in vivo. Biochemical analysis of Kv2.1 in the brains of these rats shows a marked dephosphorylation of Kv2.1. In cultured rat hippocampal pyramidal neurons, glutamate stimulation rapidly causes dephosphorylation of Kv2.1, translocation of Kv2.1 from clusters to a more uniform localization, and a shift in the voltage-dependent activation of IK. An influx of Ca 2+ leading to calcineurin activation is both necessary and sufficient for these effects. Our finding that neuronal activity modifies the phosphorylation state, localization and function of Kv2.1 suggests an important link between excitatory neurotransmission and the intrinsic excitability of pyramidal neurons.",

author = "Hiroaki Misonou and Mohapatra, {Durga P.} and Park, {Eunice W.} and Victor Leung and Dongkai Zhen and Kaori Misonou and Anderson, {Anne E.} and Trimmer, {James S.}",

note = "Funding Information: We thank A. Illausky for technical assistance; G. Mandel for allowing use of equipment; P. Brehm for chemical reagents; L. Taylor for assistance in live-cell imaging; and A.C. Bonham, J. Engebrecht, M.N. Rasband and K.J. Rhodes for critically reading the manuscript. This work was supported by the National Institute of Neurological Disorders and Stroke (NIH/NINDS; grants NS42225 to J.S.T. and NS39943 to A.E.A.).",

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AU - Mohapatra, Durga P.

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AU - Leung, Victor

AU - Zhen, Dongkai

AU - Misonou, Kaori

AU - Anderson, Anne E.

AU - Trimmer, James S.

N1 - Funding Information: We thank A. Illausky for technical assistance; G. Mandel for allowing use of equipment; P. Brehm for chemical reagents; L. Taylor for assistance in live-cell imaging; and A.C. Bonham, J. Engebrecht, M.N. Rasband and K.J. Rhodes for critically reading the manuscript. This work was supported by the National Institute of Neurological Disorders and Stroke (NIH/NINDS; grants NS42225 to J.S.T. and NS39943 to A.E.A.).

PY - 2004/7

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N2 - Voltage-dependent Kv2.1 K+ channels, which mediate delayed rectifier Kv currents (IK), are expressed in large clusters on the somata and dendrites of principal pyramidal neurons, where they regulate neuronal excitability. Here we report activity-dependent changes in the localization and biophysical properties of Kv2.1. In the kainate model of continuous seizures in rat, we find a loss of Kv2.1 clustering in pyramidal neurons in vivo. Biochemical analysis of Kv2.1 in the brains of these rats shows a marked dephosphorylation of Kv2.1. In cultured rat hippocampal pyramidal neurons, glutamate stimulation rapidly causes dephosphorylation of Kv2.1, translocation of Kv2.1 from clusters to a more uniform localization, and a shift in the voltage-dependent activation of IK. An influx of Ca 2+ leading to calcineurin activation is both necessary and sufficient for these effects. Our finding that neuronal activity modifies the phosphorylation state, localization and function of Kv2.1 suggests an important link between excitatory neurotransmission and the intrinsic excitability of pyramidal neurons.

AB - Voltage-dependent Kv2.1 K+ channels, which mediate delayed rectifier Kv currents (IK), are expressed in large clusters on the somata and dendrites of principal pyramidal neurons, where they regulate neuronal excitability. Here we report activity-dependent changes in the localization and biophysical properties of Kv2.1. In the kainate model of continuous seizures in rat, we find a loss of Kv2.1 clustering in pyramidal neurons in vivo. Biochemical analysis of Kv2.1 in the brains of these rats shows a marked dephosphorylation of Kv2.1. In cultured rat hippocampal pyramidal neurons, glutamate stimulation rapidly causes dephosphorylation of Kv2.1, translocation of Kv2.1 from clusters to a more uniform localization, and a shift in the voltage-dependent activation of IK. An influx of Ca 2+ leading to calcineurin activation is both necessary and sufficient for these effects. Our finding that neuronal activity modifies the phosphorylation state, localization and function of Kv2.1 suggests an important link between excitatory neurotransmission and the intrinsic excitability of pyramidal neurons.

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Regulation of ion channel localization and phosphorylation by neuronal activity

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