Inhibition of BKCa negatively alters cardiovascular function.

Nishi H Patel, Justin Johannesen, Kajol Shah, Sumanta K Goswami, Neel J Patel, Devasena Ponnalagu, Andrew R Kohut, Harpreet Singh

Physiological reports 2018 Jun

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Large conductance calcium and voltage-activated potassium channels (BKCa ) are transmembrane proteins, ubiquitously expressed in the majority of organs, and play an active role in regulating cellular physiology. In the heart, BKCa 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 BKCa channels results in membrane hyperpolarization which eventually results in vasodilation mediated by a reduction in Ca2+ influx due to the closure of voltage-dependent Ca2+ channels. Ex vivo studies have shown that BKCa channels play an active role in the regulation of the function of the majority of blood vessels. However, in vivo role of BKCa channels in cardiovascular function is not completely deciphered. Here, we have evaluated the rapid in vivo role of BKCa channels in regulating the cardiovascular function by using two well-established, rapid-acting, potent blockers, paxilline and iberiotoxin. Our results show that BKCa 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 BKCa channels by blockers is completely reversible, and hence, BKCa channels can be exploited as potential targets for clinical applications for modulating heart rate and cardiac contractility. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Citation

Nishi H Patel, Justin Johannesen, Kajol Shah, Sumanta K Goswami, Neel J Patel, Devasena Ponnalagu, Andrew R Kohut, Harpreet Singh. Inhibition of BKCa negatively alters cardiovascular function. Physiological reports. 2018 Jun;6(12):e13748