Update on vascular endothelial Ca2+ signalling: A tale of ion channels, pumps and transporters

Abstract

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and forms a multifunctional transducing organ that mediates a plethora of cardiovascular processes. The activation of ECs from as state of quiescence is, therefore, regarded among the early events leading to the onset and progression of potentially lethal diseases, such as hypertension, myocardial infarction, brain stroke, and tumor. Intracellular Ca²⁺ signals have long been know to play a central role in the complex network of signaling pathways regulating the endothelial functions. Notably, recent work has outlined how any change in the pattern of expression of endothelial channels, transporters and pumps involved in the modulation of intracellular Ca²⁺ levels may dramatically affect whole body homeostasis. Vascular ECs may react to both mechanical and chemical stimuli by generating a variety of intracellular Ca²⁺ signals, ranging from brief, localized Ca²⁺ pulses to prolonged Ca²⁺ oscillations engulfing the whole cytoplasm. The well-defined spatiotemporal profile of the subcellular Ca²⁺ signals elicited in ECs by specific extracellular inputs depends on the interaction between Ca²⁺ releasing channels, which are located both on the plasma membrane and in a number of intracellular organelles, and Ca²⁺ removing systems. The present article aims to summarize both the past and recent literature in the field to provide a clear-cut picture of our current knowledge on the molecular nature and the role played by the components of the Ca²⁺ machinery in vascular ECs under both physiological and pathological conditions.

Keywords: Endothelial cells; Ca²⁺ signalling; Plasma membrane; Endoplasmic reticulum; Intracellular Ca²⁺ release; Ca²⁺ entry; Ca²⁺ removal; Ca²⁺ oscillations