Dynamic Blood Flow Control in Heart

Abstract

Perfusion of the heart by blood is essential for the maintenance of physiological function. Published experiments and investigations by others reveal that the maximum AV O2 difference that can be achieved in heart is always observed between the coronary arteries and the venous outflow at the coronary sinus over the full range of blood flow (∼five fold) that is achieved. If so, exquisite matching of blood flow and O2 consumption must exist even at the smallest unit of perfusion. How does such tight control occur? We have examined the hypothesis put forward for the brain to determine if, in principle, it could work in heart. Nelson and colleagues have suggested that electrical activity could be a primary regulator of blood flow in the brain. Increased neuronal activity would lead to an increase in K+ efflux that would bathe endothelial cells which possess inward rectifier potassium channels (Kir). Activation of Kir could lead to hyperpolarization given the N-shaped Kir current-voltage (IV) relationship that we have observed. In the current study, we examined human microvascular endothelial cells from heart (HMVEC-C) in culture to determine how they responded to elevated [K+]o. We found that extracellular increases of K+ (from 5 mM to 15 mM) cause HMVEC-C hyperpolarization. This K+-induced membrane hyperpolarization is dependent on Kir activation as evidenced by its blockade by extracellular Ba2+. These findings suggest that cardiac electrical activity could contribute to K+-dependent hyperpolarization of the endothelial cells that could hyperpolarize the pre-capillary sphincter smooth muscle cells locally and thereby contribute to activity-dependent blood flow control.