Ion channels in control of blood flow: Electrical conduction along endothelium of resistance arteries

Abstract

The regulation of tissue blood fl ow in response to the metabolic demand of parenchymal cells is effected through changes in vascular resistance as governed by arteriolar networks and their proximal feed arteries. Vasodilation and vasoconstriction must be coordinated among downstream and upstream segments to optimize blood fl ow distribution within the tissue and to attain maximal perfusion of the vascular supply. Such coordinated vasomotor activity is promoted by the transmission of electrical signals (e.g., hyperpolarization and depolarization) through gap junctions from cell-to-cell along the vessel wall. Based upon underlying structural and functional relationships, we explore the biophysical basis of intercellular electrical signaling along the endothelium of resistance arteries. The endothelium is presented as a cable, whereby electrical signals decay passively with distance from the site of initiation. Key to our fi ndings is how K + channels expressed constitutively in endothelial cell membranes [e.g., K Ca2.3 (SK Ca) and K Ca3.1 (IK Ca)] regulate the spatial domain of electrical signal transmission and how this role is effected during advanced age through the actions of hydrogen peroxide. New insights into the regulation of electrical conduction along microvascular endothelium advance our understanding of how blood fl ow is governed by ion channels while providing mechanistic insight into how such processes can be affected during vascular disease.