Dynamic blood flow control by ATP‐sensitive K+ channel in heart

Abstract

Blood flow within the heart itself is tightly coupled to its metabolic needs. Despite its importance, little is known about the way the local blood flow is regulated on a beat‐to‐beat basis. This study has investigated the molecular and cellular regulatory mechanisms that control blood flow in the mammalian heart using perfused mouse cardiac papillary muscle preparation as well as cultured primary ventricular myocytes and capillary endothelial cells. State‐of‐the‐art high‐speed confocal microscopes that include a combination of XY (Nipkow disk) and point‐scanner confocals have been used to monitor the functional changes of arterioles and capillaries in heart. The preparations were examined using a temperature and flow control superfusion bath and patch clamp manipulators and instrumentation. Our results suggest that hyperpolarizing current generated by ATP‐sensitive K+ channel (KATP) in cardiomyocytes may enter apposed capillary endothelial cells through gap junctions and hyperpolarize these cells. These endothelial cells may then underlie the hyperpolarization of gap‐junction‐connected arterial smooth muscle cells that relax to produce vasodilation and blood flow elevation. An additional contribution to blood flow elevation and vascular relaxation may be attributed to extracellular K+ ([K+]o) increases around the endothelial cells (from ventricular myocyte KATP and other K+ channels). The hyperpolarization of capillary endothelial cells is due to the [K+]o‐dependent activation of inward rectifier K+ channels (Kir). Thus, the activation of KATP in cardiac myocytes caused by [ATP]i drop and/or metabolite accumulation in cardiac myocytes links the metabolism of specific myocytes to the local increase in blood flow. This mechanism is a classic negative‐feedback signaling mechanism that links ventricular myocyte metabolism to locally increased blood flow.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.