Endothelial Cell K⁺ Channels, Membrane Potential and the Release of Vasoactive Factors from the Vascular Endothelium

Abstract

Potassium channels play an important role in the regulation of the membrane potential (E _m ) of endothelial cells and thereby modulate the entry of extracellular Ca²⁺ (Adams, 1994; Himmel et al., 1993; Adams et al., 1989). Ca²⁺ entry in concert with intracellular Ca²⁺ release is important for the synthesis of a number of endothelium-derived vasoactive factors. Thus, the synthesis of the endothelium-derived relaxing factor (EDRF), nitric oxide (NO), and of prostacyclin (PGI₂) requires, respectively, the Ca²⁺-calmodulin-dependent activation of the constitutive endothelial cell nitric oxide synthase (eNOS) and the Ca²⁺ -dependent activation of phospholipase A₂ (Pollock et al., 1991; Bredt and Snyder, 1990; Carter et al., 1988; Hallam et al., 1988). Similarly, the synthesis of the vasoconstrictor peptide endothelin-1 (ET-1) requires the mobilization of intracellular Ca²⁺ and the activation of protein kinase C (Yanagisawa et al., 1989).