title: Negative News: Cl- and HCO3- in the Vascular Wall.
abstract: 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, Ca(2+)-activated Cl(-) channels, volume-regulated anion channels, and CFTR) and sensing (e.g., via WNK and RPTPγ) of Cl(-) and HCO3 (-) influence cardiovascular health and disease.
authors: Department of Biomedicine, Aarhus University, Denmark;
authors: Ebbe
authors: 0000-0002-5078-9279
authors: E
authors: Boedtkjer
authors: Department of Biomedicine, Aarhus University, Denmark;
authors: Vladimir V
authors: VV
authors: Matchkov
authors: Department of Biomedicine, Aarhus University, Denmark; Department of Clinical Medicine, Aarhus University, Denmark; and.
authors: Donna M B
authors: DM
authors: Boedtkjer
authors: Department of Biomedicine, Aarhus University, Denmark; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark eb@biomed.au.dk.
authors: Christian
authors: C
authors: Aalkjaer
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D018118:Chloride Channels / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000378:metabolism; D027982:Sodium-Bicarbonate Symporters / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism
chemical_list: D001639:Bicarbonates; D018118:Chloride Channels; D002712:Chlorides; D026901:Membrane Transport Proteins; C422022:SLC4A7 protein, human; D027982:Sodium-Bicarbonate Symporters; D064506:Solute Carrier Family 12, Member 2; D050994:Voltage-Dependent Anion Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D017346:Protein Serine-Threonine Kinases; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5