Abstract
Large conductance calcium and voltage-activated potassium channels (BK(C)(a) ) are transmembrane proteins, ubiquitously expressed in the majority of organs, and play an active role in regulating cellular physiology. In the heart, BK(C)(a) channels are known to play a role in regulating the heart rate and protect it from ischemia-reperfusion injury. In vascular smooth muscle cells, the opening of BK(C)(a) channels results in membrane hyperpolarization which eventually results in vasodilation mediated by a reduction in Ca(2+) influx due to the closure of voltage-dependent Ca(2+) channels. Ex vivo studies have shown that BK(C)(a) channels play an active role in the regulation of the function of the majority of blood vessels. However, in vivo role of BK(C)(a) channels in cardiovascular function is not completely deciphered. Here, we have evaluated the rapid in vivo role of BK(C)(a) channels in regulating the cardiovascular function by using two well-established, rapid-acting, potent blockers, paxilline and iberiotoxin. Our results show that BK(C)(a) channels are actively involved in regulating the heart rate, the function of the left and right heart as well as major vessels. We also found that the effect on BK(C)(a) channels by blockers is completely reversible, and hence, BK(C)(a) channels can be exploited as potential targets for clinical applications for modulating heart rate and cardiac contractility.