Bidirectional activity-dependent regulation of neuronal ion channel phosphorylation

Hiroaki Misonou, Milena Menegola, Durga P. Mohapatra, Lauren K. Guy, Kang Sik Park, James Trimmer

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)13505-13514
Number of pages10
JournalJournal of Neuroscience
Volume26
Issue number52
DOIs
StatePublished - Dec 27 2006

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Ion Channels
Phosphorylation
Calcineurin
Neurons
Kainic Acid
Biosensing Techniques
Serine
Anesthetics
Glutamic Acid
Digestion
Seizures

Keywords

  • Calcineurin
  • Calcium
  • Hippocampus
  • Intracellular signaling
  • Kv2.1
  • Potassium channel

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Misonou, H., Menegola, M., Mohapatra, D. P., Guy, L. K., Park, K. S., & Trimmer, J. (2006). Bidirectional activity-dependent regulation of neuronal ion channel phosphorylation. Journal of Neuroscience, 26(52), 13505-13514. https://doi.org/10.1523/JNEUROSCI.3970-06.2006

Bidirectional activity-dependent regulation of neuronal ion channel phosphorylation. / Misonou, Hiroaki; Menegola, Milena; Mohapatra, Durga P.; Guy, Lauren K.; Park, Kang Sik; Trimmer, James.

In: Journal of Neuroscience, Vol. 26, No. 52, 27.12.2006, p. 13505-13514.

Research output: Contribution to journalArticle

Misonou, H, Menegola, M, Mohapatra, DP, Guy, LK, Park, KS & Trimmer, J 2006, 'Bidirectional activity-dependent regulation of neuronal ion channel phosphorylation', Journal of Neuroscience, vol. 26, no. 52, pp. 13505-13514. https://doi.org/10.1523/JNEUROSCI.3970-06.2006
Misonou, Hiroaki ; Menegola, Milena ; Mohapatra, Durga P. ; Guy, Lauren K. ; Park, Kang Sik ; Trimmer, James. / Bidirectional activity-dependent regulation of neuronal ion channel phosphorylation. In: Journal of Neuroscience. 2006 ; Vol. 26, No. 52. pp. 13505-13514.
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