Studies performed to elucidate the inhibitory mechanisms of the hyperpolarization induced by K+ channel openers on the Call movements and force of contraction produced by either the stimulation of thromboxane A2 receptors or depolarization with high KCl have shown the follow ing: When the plasma membrane is hyperpolarized by K+ channel openers, voltage-dependent L type Ca2+ channels are deactivated and the influx of Ca2+ is decreased, as is the case with the KCl induced Call influx. The hyperpolarization of the plasma membrane also has other inhibito-ry effects on phospholipase C, a membrane-associated enzyme activity. The IP3 production and IP3 induced Ca2+ release from intracellular stores, which is related to the stimulation of the agonist receptors, are inhibited by the hyperpolarization of the plasma membrane by K+ channel openers. Recently, we showed that the Ca2+ sensitivity of the contractile elements was voltage dependent. Furthermore, membrane hyperpolarization induced by various K+ channel openers relaxed ca nine coronary arteries more profoundly than decreased [Ca2+]i. Thus, the membrane voltage may regulate intracellular enzyme activities, including contractile elements. Therefore, this new facet of signal transduction should be considered in the control of vascular tone. The evolutional rela tionships of various K+ channels are also discussed.
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