Contribution of sarcoplasmic reticulum Ca2+ to the activation of Ca2+-activated K+ channels in the resting state of arteries from spontaneously hypertensive rats

Objective Localized release of Ca2+ from the sarcoplasmic reticulum (SR) toward the plasmalemma, sometimes visualized as Ca2+ sparks, can activate Ca2+. activated K+ (K-Ca) channels. We have already reported that the addition of charybdotoxin (ChTX), a blocker of K-Ca channels, to the resting state of arteries from spontaneously hypertensive rats (SHR) caused a powerful contraction, suggesting that K-Ca, channels were active in the resting state. This study aimed to determine whether the Ca2+ responsible for activity of K-Ca channels was derived from SR. Methods Possible mechanisms underlying the ChTX-induced contractions were examined in endothelium-denuded strips of femoral, mesenteric, small mesenteric and carotid arteries from 13-week-old SHR and normotensive Wistar-Kyoto (WKY) rats by using selective inhibitors of the Ca2+ spark process. Results ChTX (100 nmol/l) induced a contraction in the SHR arteries. The ChTX-induced contractions were increased by a moderate membrane depolarization by 15.9 mmol/l K+ and were abolished by nifedipine (100 nmol/l). When SR Ca2+ was depleted by treatment of the strips with ryanodine (10 mumol/l) plus caffeine (20 mmol/1) or with thapsigargin (100 nmol/l), the ChTX-induced contraction was decreased in femoral, mesenteric and small mesenteric arteries and was almost abolished in the carotid artery. A similar phenomenon can be observed in arteries from WKY rats after a moderate membrane depolarization. In both SHR and WKY rats, SR Ca2+. dependent ChTX-induced contraction always represents 20-30% of the maximal K+-induced contraction. We conclude that activation of K-Ca channels depended upon influx of Ca2+ through L-type Ca2+ channels and release of Ca2+ from the SR, suggesting that recycling of entering Ca2+ from the superficial SR toward the plasmalemma sufficiently elevated Ca2+ near these channels to activate them. (C) 2002 Lippincott Williams Wilkins.