Activation of protein kinase C alters voltage dependence of a Na+ channel.
Phorbol esters and purified protein kinase C (PKC) have been shown to down-modulate the voltage-dependent Na+ channels expressed in Xenopus oocytes injected with chick brain RNA. We used the two-electrode voltage-clamp technique to demonstrate that a Na+ channel expressed in oocytes injected with RNA coding for the alpha subunit of the channel alone (VA200, a variant of rat brain type IIA) is also inhibited by PKC activation. The inhibition of Na+ currents, expressed in oocytes injected with either alpha subunit RNA (rat) or total brain RNA (chick), is voltage-dependent, being stronger at negative potentials. It appears to result mainly from a shift in the activation curve to the right and possibly a decrease in the steepness of the voltage dependence of activation. There is little effect on the inactivation process and maximal Na+ conductance. Thus, PKC modulates the Na+ channel by a mechanism involving changes in voltage-dependent properties of its main, channel-forming alpha subunit.
Dascal
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Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Lotan
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I
D000818:Animals; D001923:Brain Chemistry; D002642:Chick Embryo; D004553:Electric Conductivity; D004594:Electrophysiology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D009865:Oocytes / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D012313:RNA / Q000235:genetics; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014162:Transfection; D014982:Xenopus laevis
D015222:Sodium Channels; D013779:Tetrodotoxin; D012313:RNA; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate