The role of the sarcolemmal Ca2+-ATPase in the pH transients associated with contraction in rat smooth muscle

1. We have investigated the origin of the intracellular acid pH transients that accompany myometrial contraction. Intra- and extracellular pH were measured with SNARF and intra cellular Ca2+ concentration ([Ca2+](i)) with indo-1. 2. An intracellular acidification accompanied spontaneous contractions and those elicited by KCl depolarization or the addition of the agonists carbachol or prostaglandin F(2α). The size of the acidification increased with the magnitude of the contraction. 3. The intracellular acidification was accompanied by an extracellular alkalinization, showing that it results from proton movement across the surface membrane. Furthermore, it was decreased either by addition of Cd2+ (20 nM, an inhibitor of the sarcolemmal Ca2+-ATPase) or by elevating [Ca2+](o). 4. Extracellular alkalinization increased the magnitude of the rise of [Ca2+](i) and force produced by KCl. 5. An intracellular acidification was also associated with contraction in the portal vein and ureter. 6. We conclude that the sarcolemmal Ca2+-ATPase produces a significant intracellular acidification while removing Ca2+. Both the acidification and decrease of [Ca2+](i) will promote relaxation. Since Ca2+ and protons have opposite effects on many cellular processes, this dual regulation by these two ions may be of general importance.