Control of neuronal excitability by phosphorylation and dephosphorylation of sodium channels.
Currents through voltage-gated sodium channels drive action potential depolarization in neurons and other excitable cells. Smaller currents through these channels are key components of currents that control neuronal firing and signal integration. Changes in sodium current have profound effects on neuronal firing. Sodium channels are controlled by neuromodulators acting through phosphorylation of the channel by serine/threonine and tyrosine protein kinases. That phosphorylation requires specific molecular interaction of kinases and phosphatases with the channel molecule to form localized signalling complexes. Such localization is required for effective neurotransmitter-mediated regulation of sodium channels by protein kinase A. Analogous molecular complexes between sodium channels, kinases and other signalling molecules are expected to be necessary for specific and localized transmitter-mediated modulation of sodium channels by other protein kinases.
Scheuer
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Department of Pharmacology, Mailstop 357280, University of Washington, Seattle, WA 98195-7280, USA. Scheuer@u.washington.edu
Catterall
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WA
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D009474:Neurons / Q000502:physiology*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011487:Protein Conformation; D011493:Protein Kinase C / Q000378:metabolism; D015222:Sodium Channels / Q000737:chemistry / Q000502:physiology*
D015222:Sodium Channels; D019000:Phosphotyrosine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C