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Graded Regulation of the Kv2.1 Potassium Channel by Variable Phosphorylation
Kang-Sik Park,*Durga P. Mohapatra,*Hiroaki Misonou,James S. Trimmer
Dynamic modulation of ion channels by phosphorylation underliesneuronal plasticity. The Kv2.1 potassium channel is highly phosphorylatedin resting mammalian neurons. Activity-dependent Kv2.1 dephosphorylationby calcineurin induces graded hyperpolarizing shifts in voltage-dependentactivation, causing suppression of neuronal excitability. Massspectrometry–SILAC (stable isotope labeling with aminoacids in cell culture) identified 16 Kv2.1 phosphorylation sites,of which 7 were dephosphorylated by calcineurin. Mutation ofindividual calcineurin-regulated sites to alanine produced incrementalshifts mimicking dephosphorylation, whereas mutation to aspartateyielded equivalent resistance to calcineurin. Mutations at multiplesites were additive, showing that variable phosphorylation ofKv2.1 at a large number of sites allows graded activity-dependentregulation of channel gating and neuronal firing properties.
Department of Pharmacology, School of Medicine, University of California, Davis, CA 95616, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed at the Department of Pharmacology, School of Medicine 3502 GBSF, 451 East Health Sciences Drive, University of California, Davis, CA 95616, USA. E-mail: jtrimmer{at}ucdavis.edu
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To whom correspondence should be addressed at the Department of Pharmacology, School of Medicine 3502 GBSF, 451 East Health Sciences Drive, University of California, Davis, CA 95616, USA. E-mail: 
