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 α 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 a 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 a sub-unit.