Chloride channels in endothelial cells

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.