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Physiol Rep. 2018 Jun;6(12):e13748. doi: 10.14814/phy2.13748.

Inhibition of BKCa negatively alters cardiovascular function.

Author information

1
Department of Internal Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania.
2
Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania.
3
Penn Heart and Vascular Center, University of Pennsylvania, Philadelphia, Pennsylvania.
4
Division of Cardiology, Drexel University College of Medicine, Philadelphia, Pennsylvania.

Abstract

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.

KEYWORDS:

BKCa channels; cardiac function; echocardiography; paxilline

PMID:
29932499
PMCID:
PMC6014461
DOI:
10.14814/phy2.13748
[Indexed for MEDLINE]
Free PMC Article

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