Negative News: Cl- and HCO3- in the Vascular Wall

Cl- and HCO3- are the most prevalent membrane-permeable anions in the intra-and extracellular spaces of the vascular wall. Outwardly directed electrochemical gradients for Cl- and HCO3- permit anion channel opening to depolarize vascular smooth muscle and endothelial cells. Transporters and channels for Cl- and HCO3- also modify vascular contractility and structure independently of membrane potential. Transport of HCO3- regulates intracellular pH and thereby modifies the activity of enzymes, ion channels, and receptors. There is also evidence that Cl- and HCO3- transport proteins affect gene expression and protein trafficking. Considering the extensive implications of Cl- and HCO3- in the vascular wall, it is critical to understand how these ions are transported under physiological conditions and how disturbances in their transport can contribute to disease development. Recently, sensing mechanisms for Cl- and HCO3- have been identified in the vascular wall where they modify ion transport and vasomotor function, for instance, during metabolic disturbances. This review discusses current evidence that transport (e.g., via NKCC1, NBCn1, Ca2+-activated Cl- channels, volume-regulated anion channels, and CFTR) and sensing (e.g., via WNK and RPTP gamma) of Cl- and HCO3- influence cardiovascular health and disease.