Functional role of charybdotoxin-sensitive K+ channels in the resting state of cerebral, coronary and mesenteric arteries of the dog
Asano, M.; Masuzawa-Ito, K.; Matsuda, T.; Suzuki, Y.; Oyama, H.; Shibuya, M.; Sugita, K.
Journal of Pharmacology and Experimental Therapeutics 267(3): 1277-1285
1993
ISSN/ISBN: 0022-3565 PMID: 7505329 Document Number: 418186
To determine the possible role of Ca++-activated K+ (K-Ca) channels in the regulation of resting tone of arteries, the effects of agents that interact with these channels on tension and 86Rb efflux were examined in endothelium-denuded strips of cerebral (middle cerebral, posterior cerebral and basilar), coronary and mesenteric arteries of the dog. Strips of cerebral arteries maintained a myogenic tone; ie., the resting tone decreased when either the Krebs' solution was replaced with a Ca++-free solution or nifedipine was added. The addition of charybdotoxin, a blocker of large conductance K-Ca channels, to the resting strips (strips at a resting state) caused a concentration-dependent contraction in the cerebral arteries but not in the coronary or mesenteric artery. In resting strips preloaded with 86Rb, the basal 86Rb efflux rate constant was significantly greater in the cerebral arteries than in the coronary and mesenteric arteries. The addition of nifedipine to the resting strips decreased the basal 86Rb efflux rate constant in the cerebral and coronary arteries. Effects of nifedipine on tension and 86Rb efflux in 20.9 mM K+-contracted strips of the mesenteric artery were comparable to the effects of this blocker in the resting strips of the middle cerebral artery. The 86Rb efflux rate constant during the stimulation with 65.9 mM K+ was similar for the middle cerebral and mesenteric arteries. Studies using 1- or 5-min pulse labeling with 45Ca demonstrated increased basal 45Ca influx in the resting state of cerebral arteries compared with the coronary and mesenteric arteries. Bay k 8644, a dihydropyridine Ca++ agonist, elicited greater contraction in the middle cerebral artery than in the mesenteric artery. The results suggest that the charybdotoxin-sensitive K-Ca channels regulate the myogenic tone in the resting state of cerebral arteries. The high activation of K-Ca channels in the cerebral arteries appears to be secondary to the increased transmembrane Ca++ influx, probably through the activation of L-type voltage-dependent Ca++ channels in the resting state of these arteries.