Graded Regulation of the Kv2.1 Potassium Channel by Variable Phosphorylation

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, cau...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2006-08, Vol.313 (5789), p.976-979
Main Authors: Park, Kang-Sik, Mohapatra, Durga P, Misonou, Hiroaki, Trimmer, James S
Format: Article
Language:English
Subjects:
Alanine - genetics
Alanine - metabolism
Alkaline Phosphatase - metabolism
Amino acids
Animals
Aspartic Acid - genetics
Aspartic Acid - metabolism
Biochemistry
Biological and medical sciences
Brain - metabolism
Calcineurin - metabolism
Calcium - metabolism
Cell Line
Chromatography, Liquid
Fundamental and applied biological sciences. Psychology
HEK293 cells
Humans
Ion Channel Gating
Ionomycin - pharmacology
Ions
Mass Spectrometry
Mutation
Neurons
Neurons - physiology
Neuroscience
Neurosciences
Patch-Clamp Techniques
Phosphorylation
Phosphoserine - metabolism
Phosphothreonine - metabolism
Physiological regulation
Point Mutation
Post traumatic stress disorder
Potassium
Rats
Recombinant Proteins - metabolism
Serine - genetics
Shab Potassium Channels - metabolism
Transfection
Vertebrates: nervous system and sense organs
Veterans
War
Warfare
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1124254