EFFECT OF INTRACELLULAR PH ON FERRET PULMONARY ARTERIAL SMOOTH-MUSCLECELL CALCIUM HOMEOSTASIS AND PRESSURE

In this study, we investigated the role of Na+/H+ antiport in regulati ng cytosolic (intracellular) pH (pH(i)) in isolated and cultured ferre t pulmonary arterial smooth muscle cells (PSMC). We also studied the e ffects of modulating pH(i) on the cytosolic (intracellular) calcium co ncentration ([Ca2+](i)) in the PSMC and on the pulmonary arterial pres sure (Ppa) of isolated ferret lungs. pH(i) 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. Block ing the Na+/H+ antiporter decreased baseline pH(i) and prevented the r ecovery from NH4Cl washout-induced intracellular acidosis. Intracellul ar alkalinization caused an initial transient increase in both [Ca2+]( i) and Ppa that were dependent on extracellular Ca2+ entry. Maintainin g 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-induc ed increase in [Ca2+](i) and Ppa were mediated by both extracellular C a2+ influx and release of stored intracellular Ca2+. Cytosolic acidosi s also appears to have a direct effect on the smooth muscle contractil e elements. Both cytosolic alkalosis and acidosis increased vascular r eactivity.