PubMed 17192433

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kv2.1

Title: Bidirectional activity-dependent regulation of neuronal ion channel phosphorylation.

Authors: Hiroaki Misonou, Milena Menegola, Durga P Mohapatra, Lauren K Guy, Kang-Sik Park, James S Trimmer

Journal, date & volume: J. Neurosci., 2006 Dec 27 , 26, 13505-14

PubMed link:

Activity-dependent dephosphorylation of neuronal Kv2.1 channels yields hyperpolarizing shifts in their voltage-dependent activation and homoeostatic suppression of neuronal excitability. We recently identified 16 phosphorylation sites that modulate Kv2.1 function. Here, we show that in mammalian neurons, compared with other regulated sites, such as serine (S)563, phosphorylation at S603 is supersensitive to calcineurin-mediated dephosphorylation in response to kainate-induced seizures in vivo, and brief glutamate stimulation of cultured hippocampal neurons. In vitro calcineurin digestion shows that supersensitivity of S603 dephosphorylation is an inherent property of Kv2.1. Conversely, suppression of neuronal activity by anesthetic in vivo causes hyperphosphorylation at S603 but not S563. Distinct regulation of individual phosphorylation sites allows for graded and bidirectional homeostatic regulation of Kv2.1 function. S603 phosphorylation represents a sensitive bidirectional biosensor of neuronal activity.