TY - JOUR
T1 - Negative News
T2 - Cl- and HCO3- in the Vascular Wall
AU - Bødtkjer, Ebbe
AU - Matchkov, Vladimir V
AU - Boedtkjer, Donna M B
AU - Aalkjaer, Christian
N1 - ©2016 Int. Union Physiol. Sci./Am. Physiol. Soc.
PY - 2016/9
Y1 - 2016/9
N2 - 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 RPTPλ) of Cl− and HCO3− influence cardiovascular health and disease.
AB - 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 RPTPλ) of Cl− and HCO3− influence cardiovascular health and disease.
U2 - 10.1152/physiol.00001.2016
DO - 10.1152/physiol.00001.2016
M3 - Review
C2 - 27511463
SN - 1548-9213
VL - 31
SP - 370
EP - 383
JO - Physiology
JF - Physiology
IS - 5
ER -