Phosphorylation at a Single Site in the Rat Brain Sodium Channel Is Necessary and Sufficient for Current Reduction by Protein

Voltage-gated sodium channels respond to excitatory inputs in nerve cells, generating spikes of depolarization at axon hillock regions and propagating the initial rising phase of action po-tentials through axons. It previously has been shown that pro-tein kinase A (PKA) attenuates sodium current amplitude 20– 50 % by phosphorylating serines located in the I–II linker of the sodium channel. We have tested the individual contributions of five PKA consensus sites in the I–II linker by measuring sodium currents expressed in Xenopus oocytes during conditions of PKA induction. PKA was induced by perfusing oocytes with a cocktail that contained forskolin, chlorophenylthio-cAMP, dibutyryl-cAMP, and 3-isobutyl-1-methylxanthine. Phosphory-lation at the second PKA site (serine-573) was necessary and sufficient to diminish sodium current amplitude. Phosphoryla-tion at the third and fourth positions (serine-610 and serine-623