Potentiation of rat brain sodium channel currents by PKA in Xenopus oocytes involves the I-II linker.
Functional modulation of voltage-gated sodium channels affects the electrical excitability of neurons. Protein kinase A (PKA) can decrease sodium currents by phosphorylation at consensus sites in the cytoplasmic I-II linker. Once the sites are phosphorylated, however, additional PKA activity can increase sodium currents by an unknown mechanism. When the PKA sites were eliminated by substitutions of alanine for serine, peak sodium current amplitudes were increased by 20-80% when PKA was activated in Xenopus oocytes either by stimulation of a coexpressed beta(2)-adrenergic receptor or by perfusion with reagents that increase cAMP. Potentiation required the I-II linker of the brain channel, in that a chimeric channel in which the brain linker was replaced with the comparable linker from the skeletal muscle channel did not demonstrate potentiation. Using a series of chimeric and deleted channels, we demonstrate that potentiation is not dependent on any single region of the linker and that the extent of potentiation varies depending on the total length and the residues throughout the linker. These data are consistent with the hypothesis that potentiation by PKA is an indirect process involving phosphorylation of an accessory protein that interacts with the I-II linker of the sodium channel.
Smith
R D
RD
Department of Microbiology and Molecular Genetics, University of California, Irvine, California 92697-4025, USA.
Goldin
A L
AL
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002678:Chimera; D016384:Consensus Sequence / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology*; D004357:Drug Synergism; D004553:Electric Conductivity; D004789:Enzyme Activation; D017353:Gene Deletion; D009132:Muscles / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism*; D051381:Rats; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*; D014981:Xenopus
D015222:Sodium Channels; D017868:Cyclic AMP-Dependent Protein Kinases