Modulation of vertebrate brain Na+ and K+ channels by subtypes of protein kinase C.

Effects of purified subtypes I, II and III of protein kinase C (PKC) on voltage-dependent transient K+ (A) and Na+ channels were studied in Xenopus oocytes injected with chick brain RNA. The experiments were performed in the constant presence of 10 nM beta-phorbol 12-myristate-13-acetate (PMA). Intracellular injection of subtype I (tau) reduced the A-current (IA), with no effect on Na+ current (INa). PKC subtype II (beta 1 + beta 2) and III (alpha) reduced both currents. PKC did not affect the response to kainate. Inactivated (heated) or unactivated (injected in the absence of PMA) enzyme and vehicle alone had no effect. Our results strongly suggest that INa and IA in vertebrate neurons are modulated by PKC; all PKC subtypes exert a similar effect on the A-channel while only subtypes II and III modulate the Na+ channel.