The Calcium Signaling Mechanisms in Arterial Smooth Muscle and Endothelial Cells

The contractile state of resistance arteries and arterioles is a crucial determinant of blood pressure and blood flow. Physiological regulation of arterial contractility requires constant communication between endothelial and smooth muscle cells. Various Ca²⁺ signals and Ca²⁺ -sensitive targets ensure dynamic control of intercellular communications in the vascular wall. The functional effect of a Ca²⁺ signal on arterial contractility depends on the type of Ca²⁺ -sensitive target engaged by that signal. Recent studies using advanced imaging methods have identified the spatiotemporal signatures of individual Ca²⁺ signals that control arterial and arteriolar contractility. Broadly speaking, intracellular Ca²⁺ is increased by ion channels and transporters on the plasma membrane and endoplasmic reticular membrane. Physiological roles for many vascular Ca²⁺ signals have already been confirmed, while further investigation is needed for other Ca²⁺ signals. This article focuses on endothelial and smooth muscle Ca²⁺ signaling mechanisms in resistance arteries and arterioles. We discuss the Ca²⁺ entry pathways at the plasma membrane, Ca²⁺ release signals from the intracellular stores, the functional and physiological relevance of Ca²⁺ signals, and their regulatory mechanisms. Finally, we describe the contribution of abnormal endothelial and smooth muscle Ca²⁺ signals to the pathogenesis of vascular disorders. © 2021 American Physiological Society. Compr Physiol 11:1831-1869, 2021.