title: Extracellular HCO3- is sensed by mouse cerebral arteries: Regulation of tone by receptor protein tyrosine phosphatase γ.
abstract: We investigate sensing and signaling mechanisms for H(+), [Formula: see text] and CO2 in basilar arteries using out-of-equilibrium solutions. Selectively varying pHo, [[Formula: see text]]o, or pCO2, we find: (a) lowering pHo attenuates vasoconstriction and vascular smooth muscle cell (VSMC) Ca(2+)-responses whereas raising pHo augments vasoconstriction independently of VSMC [Ca(2+)]i, (b) lowering [[Formula: see text]]o increases arterial agonist-sensitivity of tone development without affecting VSMC [Ca(2+)]i but c) no evidence that CO2 has direct net vasomotor effects. Receptor protein tyrosine phosphatase (RPTP)γ is transcribed in endothelial cells, and direct vasomotor effects of [Formula: see text] are absent in arteries from RPTPγ-knockout mice. At pHo 7.4, selective changes in [[Formula: see text]]o or pCO2 have little effect on pHi At pHo 7.1, decreased [[Formula: see text]]o or increased pCO2 causes intracellular acidification, which attenuates vasoconstriction. Under equilibrated conditions, anti-contractile effects of CO2/[Formula: see text] are endothelium-dependent and absent in arteries from RPTPγ-knockout mice. With CO2/[Formula: see text] 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 pHo and pHi inhibit vasoconstriction, whereas decreased [[Formula: see text]]o promotes vasoconstriction through RPTPγ-dependent changes in VSMC Ca(2+)-sensitivity. [Formula: see text] serves dual roles, providing substrate for pHi-regulating membrane transporters and modulating arterial responses to acid-base disturbances.
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA eb@biomed.au.dk.
authors.forename: Ebbe
authors.initials: E
authors.lastname: Boedtkjer
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Kristoffer B
authors.initials: KB
authors.lastname: Hansen
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Donna M B
authors.initials: DMB
authors.lastname: Boedtkjer
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Aalkjaer
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Walter F
authors.initials: WF
authors.lastname: Boron
mesh_terms: D000818:Animals; D001639:Bicarbonates; D002118:Calcium / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood; D002536:Cerebral Arteries / Q000502:physiology*; D042783:Endothelial Cells; D006863:Hydrogen-Ion Concentration; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000235:genetics / Q000502:physiology*; D014661:Vasoconstriction
chemical_list: D001639:Bicarbonates; D002245:Carbon Dioxide; C516851:Ptprg protein, mouse; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D002118:Calcium
keywords: Vascular biology; basic science; calcium imaging; confocal microscopy; electrophysiology; endothelium; experimental; pH; physiology; receptors; smooth muscle