Protein kinase A phosphorylation enhances sodium channel currents in Xenopus oocytes.
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.
Smith
R D
RD
Department of Microbiology and Molecular Genetics, University of California, Irvine 92717.
Goldin
A L
AL
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004594:Electrophysiology; D047908:Intracellular Signaling Peptides and Proteins; D007545:Isoproterenol / Q000494:pharmacology; D009132:Muscles / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000494:pharmacology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology*
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D011943:Receptors, Adrenergic, beta; D015222:Sodium Channels; C015482:protein kinase modulator; D003994:Bucladesine; D000242:Cyclic AMP; D011494:Protein Kinases; D010744:Phosphoric Monoester Hydrolases; D007545:Isoproterenol