Chloride channels in endothelial cells

Abstract Endothelial cells (ECs) line the lumen of blood and lymphatic vessels and form capillaries. ECs are exposed to a diverse array of physiological stimuli and regulate a multitude of functions, including contractility, blood coagulation, leukocyte recruitment, wound healing, angiogenesis and the blood–tissue exchange of gases, metabolites and macromolecules. Chloride (Cl − ) is the principal anion in ECs, with its intracellular concentration ([Cl − ] i ) regulated by pumps, transporters and channels. ECs express the Cl − channel proteins transmembrane protein 16A (TMEM16A, ANO1), leucine‐rich repeat (LRR)‐containing 8 (LRRC8), CLCs and cystic fibrosis transmembrane conductance regulator (CFTR), which are plasma membrane proteins, and CLICs, which are located on intracellular organelles. Cl − channels can regulate both the membrane potential and [Cl − ] i of ECs to modulate physiological functions. Recent evidence indicates that intracellular Cl − is a physiological second messenger that regulates the activity of WNK (i.e. with‐no‐lysine) kinases in ECs. Impaired functions of Cl – channels in ECs have also been associated with diseases such as hypertension, atherosclerosis, cancer and lung oedema. This review discusses the current knowledge of individual Cl − channel types that are expressed in ECs, as well as their signalling mechanisms, physiological functions and pathological relevance. image