Hyperpolarization and the endothelium

Abstract

The ability of vascular endothelial cells to generate and conduct membrane hyperpolarization is a critical integrative mechanism controlling local blood flow and systemic blood pressure. This mechanism is particularly apparent in the microcirculation. Hyperpolarization initiated in the endothelium by receptor activation or local influences such as K⁺ stimulates vasodilation by passive, radial current spread via heterocellular myoendothelial gap junctions (MEJs) and/or the release of a diffusible factor(s). In addition, the endothelium has high-input resistance and serves as an effective conduit, conducting hyperpolarization bidirectionally through microvascular networks. This not only coordinates vasomotor responses but also causes ascending vasodilation, both of which reduce resistance sufficiently to allow an increase in tissue blood flow. These processes will be disrupted by the endothelial dysfunction in disease, helping explain why enhanced vasoreactivity and vasospasm develops in resistance arteries, limiting blood flow into the microcirculation.