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PMID: 15195093 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

Regulation of ion channel localization and phosphorylation by neuronal activity.

Nature neuroscience ·Vol. 7 ·No. 7 ·2004-07-00 ·Pages 711-8

Misonou H, Mohapatra DP, Park EW, Leung V, Zhen D, Misonou K, Anderson AE, Trimmer JS

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.

MeSH Terms

Animals Animals, Newborn Blotting, Western Cadmium Chloride/pharmacology Calcimycin/pharmacology Calcium Channel Blockers/pharmacology Cell Count Cells, Cultured Cyclosporine/pharmacology Delayed Rectifier Potassium Channels Dendrites/drug effects,physiology Disease Models, Animal Dose-Response Relationship, Drug Drug Interactions Enzyme Inhibitors/pharmacology Excitatory Amino Acid Antagonists/pharmacology Glutamic Acid/pharmacology Hippocampus/cytology Ion Channel Gating/drug effects Ionophores/pharmacology Kainic Acid/pharmacology Membrane Potentials/drug effects,physiology Neuronal Plasticity/drug effects,physiology Nitrendipine/pharmacology Nitriles Okadaic Acid/pharmacology Patch-Clamp Techniques/methods Phosphoprotein Phosphatases/pharmacology Phosphorylation/drug effects Potassium/metabolism Potassium Channel Blockers/pharmacology Potassium Channels/metabolism Potassium Channels, Voltage-Gated Potassium Chloride/pharmacology Pyramidal Cells/drug effects,metabolism Pyrethrins/pharmacology Rats Seizures/chemically induced,physiopathology Shab Potassium Channels Time Factors Translocation, Genetic/drug effects,physiology

Chemicals

Calcium Channel Blockers Delayed Rectifier Potassium Channels Enzyme Inhibitors Excitatory Amino Acid Antagonists Ionophores Kcnb1 protein, rat Nitriles Potassium Channel Blockers Potassium Channels Potassium Channels, Voltage-Gated Pyrethrins Shab Potassium Channels Okadaic Acid decamethrin Calcimycin Glutamic Acid Potassium Chloride Cyclosporine Nitrendipine Phosphoprotein Phosphatases Cadmium Chloride Potassium Kainic Acid

Authors & Affiliations

8 authors, click to expand affiliations / ORCID

Misonou Hiroaki

Department of Pharmacology, School of Medicine, University of California, Davis, California 95616, USA. [email protected]

Mohapatra Durga P

Park Eunice W

Leung Victor

Zhen Dongkai

Misonou Kaori

Anderson Anne E

Trimmer James S

Article Info

Journal

Nature neuroscience

Abbr.

Nat Neurosci

ISSN

1097-6256

DOI

10.1038/nn1260

[email protected]

Published

2004-07-00

Epub

2004-00-13

Pages

711-8

Language

English

Region

United States

NLM ID

9809671

Subset

Grants

NINDS NIH HHS · NS39943 · United States

NINDS NIH HHS · NS42225 · United States

Corrections

CommentIn

PMID: 15220926

External Links

PubMed source DOI: 10.1038/nn1260 View journal details

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