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Science 4 October 1991:
Vol. 254. no. 5028, pp. 115 - 118
DOI: 10.1126/science.1656525
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Articles

Science, Vol 254, Issue 5028, 115-118
Copyright © 1991 by American Association for the Advancement of Science

articles

Functional modulation of brain sodium channels by protein kinase C phosphorylation

R Numann, WA Catterall, and T Scheuer

Department of Pharmacology, University of Washington, Seattle 98195.

Voltage-gated sodium channels, which are responsible for the generation of action potentials in the brain, are phosphorylated by protein kinase C (PKC) in purified form. Activation of PKC decreases peak sodium current up to 80 percent and slows its inactivation for sodium channels in rat brain neurons and for rat brain type IIA sodium channel alpha subunits heterologously expressed in Chinese hamster ovary cells. These effects are specific for PKC because they can be blocked by specific peptide inhibitors of PKC and can be reproduced by direct application of PKC to the cytoplasmic surface of sodium channels in excised inside-out membrane patches. Modulation of brain sodium channels by PKC is likely to have important effects on signal transduction and synaptic transmission in the central nervous system.


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