Blood Flow Control by ATP-Sensitive Potassium Channel in Heart

Abstract

Blood flow within the heart is tightly coupled to its metabolic needs. Despite its importance, little is known about the way the local blood flow is regulated at the molecular and cellular levels. The current study has investigated the molecular and cellular regulatory mechanisms that control blood flow in the mammalian heart using a perfused mouse cardiac papillary muscle preparation. Additionally, primary co-cultures of ventricular myocytes and capillary endothelial cells have been used. Functional changes of arterioles and capillaries in heart were examined using high-speed confocal microscopes with a combination of XY (Nipkow disk) and point-scanning imaging. The preparations were examined using a temperature and flow control superfusion bath and patch clamp instrumentation. Our results suggest that ATP-sensitive K+ channel (KATP) in cardiomyocytes are responsible for pinacidil and diazoxide induced vasodilation in papillary muscle. Additional evidence demonstrates that the hyperpolarizing current generated by cardiomyocyte KATP can be injected into the apposed capillary endothelial cells, and then into arterial smooth muscle cells, leading to vasodilation, and blood flow elevation. An additional contribution to blood flow elevation and vascular relaxation is attributed to extracellular K+ ([K+]o) increases resulted from KATP (and other K+ channels) in cardiac myocytes that lead to hyperpolarization of capillary endothelial cells through activating inward rectifier K+ channels (Kir). Thus, the activation of KATP in cardiac myocytes caused by [ATP]i drop and/or metabolites accumulation links the metabolism demanding from myocytes to the increased blood flow in microvessels together via electrical transmission of hyperpolarizing current through gap junctions and [K+]o-induced hyperpolarization of capillary endothelial cells.