Calcium and Electrical Signaling along Endothelium of the Resistance Vasculature

摘要

This MiniReview is focused on the nature of intercellular signaling along the endothelium that helps to coordinate blood flow control in vascular resistance networks. Vasodilation initiated by contracting skeletal muscle ascends from arterioles within the tissue to encompass resistance arteries upstream and thereby increase blood flow during exercise. In resistance vessels, acetylcholine microiontophoresis or intracellular current injection initiates hyperpolarization that conducts through gap junction channels (GJCs) along the vessel wall resulting in conducted vasodilation (CVD). Both ascending vasodilation and CVD are eliminated with endothelial cell (EC) disruption, pointing to common signaling events and mutual dependence upon EC integrity. As demonstrated by electrical coupling and dye transfer during intracellular recording, their longitudinal orientation and robust expression of GJCs enable ECs to play a predominant role in CVD. Once conduction is initiated, a major interest centers on whether CVD is purely passive or involves additional “active” signaling events. Here, we discuss components for Ca²⁺ and electrical signaling with an emphasis on intercellular coupling through endothelial GJCs. We stress the importance of understanding relationships between intracellular Ca²⁺ dynamics, EC hyperpolarization and CVD while integrating findings from isolated ECs into more complex interactions in vivo. Whereas endothelial dysfunction accompanies cardiovascular disease and the components of intra- and inter-cellular signaling are increasingly well defined, little is known of how Ca²⁺ signaling and electrical conduction along microvascular endothelium are altered in diseased states. Thus, greater insight into how these relationships are governed and interact is a key goal for continued research efforts.