[Hyperpolarization-relaxation coupling in vascular smooth muscle].
Studies performed to elucidate the inhibitory mechanisms of the hyperpolarization induced by K+ channel openers on the Ca2+ movements and force of contraction produced by either the stimulation of thromboxane A2 receptors or depolarization with high KCl have shown the following: 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 Ca2+ influx. The hyperpolarization of the plasma membrane also has other inhibitory 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 canine 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 relationships of various K+ channels are also discussed.
Yanagisawa
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Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002462:Cell Membrane; D004285:Dogs; D008564:Membrane Potentials; D009126:Muscle Relaxation; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D015398:Signal Transduction
D015220:Calcium Channels; D015221:Potassium Channels; D002118:Calcium