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 Trimmer

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323 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)711-718
Number of pages8
JournalNature Neuroscience
Issue number7
StatePublished - Jul 2004

ASJC Scopus subject areas

  • Neuroscience(all)


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