AJP - Cell Physiology, Vol 263, Issue 3 C660-C666, Copyright © 1992 by American Physiological Society

ARTICLES

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.

This article has been cited by other articles:

				M. J. Davis, X. Wu, T. R. Nurkiewicz, J. Kawasaki, P. Gui, M. A. Hill, and E. Wilson Regulation of ion channels by protein tyrosine phosphorylation Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H1835 - H1862. [Abstract] [Full Text] [PDF]

				D. Wicher Peptidergic Modulation of an Insect Na+ Current: Role of Protein Kinase A and Protein Kinase C J Neurophysiol, January 1, 2001; 85(1): 374 - 383. [Abstract] [Full Text] [PDF]

				E. M. Horn and T. G. Waldrop Hypoxic Augmentation of Fast-Inactivating and Persistent Sodium Currents in Rat Caudal Hypothalamic Neurons J Neurophysiol, November 1, 2000; 84(5): 2572 - 2581. [Abstract] [Full Text] [PDF]

				R. D. Smith and A. L. Goldin Potentiation of rat brain sodium channel currents by PKA in Xenopus oocytes involves the I-II linker Am J Physiol Cell Physiol, April 1, 2000; 278(4): C638 - C645. [Abstract] [Full Text] [PDF]

				S. Herzig and J. Neumann Effects of Serine/Threonine Protein Phosphatases on Ion Channels in Excitable Membranes Physiol Rev, January 1, 2000; 80(1): 173 - 210. [Abstract] [Full Text] [PDF]

				J.-F. Desaphy, A. De Luca, and D. C. Camerino Blockade by cAMP of native sodium channels of adult rat skeletal muscle fibers Am J Physiol Cell Physiol, December 1, 1998; 275(6): C1465 - C1472. [Abstract] [Full Text] [PDF]

				M. D. Hilborn, R. R. Vaillancourt, and S. G. Rane Growth Factor Receptor Tyrosine Kinases Acutely Regulate Neuronal Sodium Channels through the Src Signaling Pathway J. Neurosci., January 15, 1998; 18(2): 590 - 600. [Abstract] [Full Text] [PDF]

				L. McAnelly and H. H. Zakon Protein Kinase A Activation Increases Sodium Current Magnitude in the Electric Organ of Sternopygus J. Neurosci., July 15, 1996; 16(14): 4383 - 4388. [Abstract] [Full Text] [PDF]