AJP - Cell Physiology, Vol 263, Issue 3 C660-C666, Copyright © 1992 by American Physiological Society
Protein kinase A phosphorylation enhances sodium channel currents in Xenopus oocytes
R. D. Smith and A. L. Goldin
Department of Microbiology and Molecular Genetics, University of California, Irvine 92717.
The voltage-sensitive rat brain sodium channel is known to be
phosphorylated by adenosine 3',5'-cyclic monophosphate (cAMP)-dependent
protein kinase A (PKA), but the functional significance of that
phosphorylation is unknown. We have shown that rat brain sodium channel
currents expressed in Xenopus oocytes were enhanced by induction of PKA
activity. Stimulation of the beta 2-adrenergic receptor or treatment with
dibutyryl cAMP resulted in increased sodium current amplitudes without
affecting the voltage dependence of channel activation or inactivation.
These increases were completely blocked by preinjection of protein kinase
inhibitor, a specific inhibitor of PKA. Injection of phosphatase into the
oocytes resulted in a significant decrease in sodium current amplitude,
indicating that phosphorylation is important for basal levels of sodium
channel activity in oocytes. The enhancement was specific for the rat brain
IIA sodium channel, because currents expressed from the rat muscle microI
sodium channel were not enhanced by the same procedures. These data
demonstrate a modulatory role of PKA phosphorylation on brain sodium
channel function and suggest a means by which the electrical excitability
of cells may be regulated.
