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      Extracellular HCO3- is sensed by mouse cerebral arteries: Regulation of tone by receptor protein tyrosine phosphatase γ

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          Abstract

          We investigate sensing and signaling mechanisms for H +, HCO 3 - and CO 2 in basilar arteries using out-of-equilibrium solutions. Selectively varying pH o, [ HCO 3 - ] o, or pCO 2, we find: (a) lowering pH o attenuates vasoconstriction and vascular smooth muscle cell (VSMC) Ca 2+-responses whereas raising pH o augments vasoconstriction independently of VSMC [Ca 2+] i, (b) lowering [ HCO 3 - ] o increases arterial agonist-sensitivity of tone development without affecting VSMC [Ca 2+] i but c) no evidence that CO 2 has direct net vasomotor effects. Receptor protein tyrosine phosphatase (RPTP)γ is transcribed in endothelial cells, and direct vasomotor effects of HCO 3 o - are absent in arteries from RPTPγ-knockout mice. At pH o 7.4, selective changes in [ HCO 3 - ] o or pCO 2 have little effect on pH i. At pH o 7.1, decreased [ HCO 3 - ] o or increased pCO 2 causes intracellular acidification, which attenuates vasoconstriction. Under equilibrated conditions, anti-contractile effects of CO 2/ HCO 3 - are endothelium-dependent and absent in arteries from RPTPγ-knockout mice. With CO 2/ HCO 3 - present, contractile responses to agonist-stimulation are potentiated in arteries from RPTPγ-knockout compared to wild-type mice, and this difference is larger for respiratory than metabolic acidosis. In conclusion, decreased pH o and pH i inhibit vasoconstriction, whereas decreased [ HCO 3 - ] o promotes vasoconstriction through RPTPγ-dependent changes in VSMC Ca 2+-sensitivity. HCO 3 o - serves dual roles, providing substrate for pH i-regulating membrane transporters and modulating arterial responses to acid–base disturbances.

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          Author and article information

          Journal
          J Cereb Blood Flow Metab
          J. Cereb. Blood Flow Metab
          JCB
          spjcb
          Journal of Cerebral Blood Flow & Metabolism
          SAGE Publications (Sage UK: London, England )
          0271-678X
          1559-7016
          19 October 2015
          May 2016
          : 36
          : 5
          : 965-980
          Affiliations
          [1 ]Department of Biomedicine, Aarhus University, Aarhus, Denmark
          [2 ]Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA
          Author notes
          [*]Ebbe Boedtkjer, Department of Biomedicine, Aarhus University, Ole Worms Allé 3, Building 1170, DK-8000 Aarhus C, Denmark. Email: eb@ 123456biomed.au.dk
          Article
          PMC4853837 PMC4853837 4853837 10.1177_0271678X15610787
          10.1177/0271678X15610787
          4853837
          26661205
          df896dfd-079b-4b9d-bd36-a2ff7bc31793
          © The Author(s) 2015
          Categories
          Original Articles

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