Graded regulation of the Kv2.1 potassium channel by variable phosphorylation

Kang Sik Park, Durga P. Mohapatra, Hiroaki Misonou, James S. Trimmer

Research output: Contribution to journalArticle

203 Scopus citations

Abstract

Dynamic modulation of ion channels by phosphorylation underlies neuronal plasticity. The Kv2.1 potassium channel is highly phosphorylated in resting mammalian neurons. Activity-dependent Kv2.1 dephosphorylation by calcineurin induces graded hyperpolarizing shifts in voltage-dependent activation, causing suppression of neuronal excitability. Mass spectrometry-SILAC (stable isotope labeling with amino acids in cell culture) identified 16 Kv2.1 phosphorylation sites, of which 7 were dephosphorylated by calcineurin. Mutation of individual calcineurin-regulated sites to alanine produced incremental shifts mimicking dephosphorylation, whereas mutation to aspartate yielded equivalent resistance to calcineurin. Mutations at multiple sites were additive, showing that variable phosphorylation of Kv2.1 at a large number of sites allows graded activity-dependent regulation of channel gating and neuronal firing properties.

Original languageEnglish
Pages (from-to)976-979
Number of pages4
JournalScience
Volume313
Issue number5789
DOIs
StatePublished - Aug 18 2006

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    Park, K. S., Mohapatra, D. P., Misonou, H., & Trimmer, J. S. (2006). Graded regulation of the Kv2.1 potassium channel by variable phosphorylation. Science, 313(5789), 976-979. https://doi.org/10.1126/science.1124254