Effect of intracellular pH on ferret pulmonary arterial smooth muscle cell calcium homeostasis and pressure.
In this study, we investigated the role of Na+/H+ antiport in regulating cytosolic (intracellular) pH (pHi) in isolated and cultured ferret pulmonary arterial smooth muscle cells (PSMC). We also studied the effects of modulating pHi on the cytosolic (intracellular) calcium concentration ([Ca2+]i) in the PSMC and on the pulmonary arterial pressure (Ppa) of isolated ferret lungs. pHi was modulated by the NH4Cl washout method. To eliminate the contribution of Cl-/HCO3- exchangers, the PSMC and isolated lungs were perfused in HCO3- free buffer. Blocking the Na+/H+ antiporter decreased baseline pHi and prevented the recovery from NH4Cl washout-induced intracellular acidosis. Intracellular alkalinization caused an initial transient increase in both [Ca2+]i and Ppa that were dependent on extracellular Ca2+ entry. Maintaining cytosolic alkalinization caused another increase in Ppa that was not associated with an increase in [Ca2+]i. Intracellular acidosis also caused an increase in [Ca2+]i and Ppa. The cytosolic acidosis-induced increase in [Ca2+]i and Ppa were mediated by both extracellular Ca2+ influx and release of stored intracellular Ca2+. Cytosolic acidosis also appears to have a direct effect on the smooth muscle contractile elements. Both cytosolic alkalosis and acidosis increased vascular reactivity.
Farrukh
I S
IS
Division of Respiratory, Critical Care, and Occupational Medicine, Veterans Affairs Medical Center and University of Utah Health Science Center, Salt Lake City 84132, USA.
Hoidal
J R
JR
Barry
W H
WH
D000138:Acidosis / Q000378:metabolism; D000471:Alkalosis / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005289:Ferrets / Q000502:physiology*; D005452:Fluoresceins; D005453:Fluorescence; D005456:Fluorescent Dyes; D006706:Homeostasis / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007211:Indoles; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009129:Muscle Tonus / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D014661:Vasoconstriction / Q000502:physiology
D005452:Fluoresceins; D005456:Fluorescent Dyes; D007211:Indoles; D017923:Sodium-Hydrogen Exchangers; D011189:Potassium Chloride; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; D012964:Sodium; C048960:indo-1; D002118:Calcium