The effects of extracellular and intracellular pH on intracellular Ca2+ regulation in guinea-pig detrusor smooth muscle.

1. Intracellular pH (pHi) and intracellular [Ca2+] ([Ca2+]i) were measured during changes to superfusate PCO2 and/or [NaHCO3]. Changes to superfusate PCO2 produced sustained changes to pHi and [Ca2+]i, while changes to [NaHCO3] altered only extracellular pH (pHo). 2. Carbachol or caffeine induced a transient rise of [Ca2+]i due to Ca2+ release from an intracellular store. This Ca2+ transient was reduced by extracellular acidosis, but increased by intracellular acidosis. Alkalosis in either compartment produced opposite effects to acidosis. Changes to the Ca2+ transient mirrored those to phasic tension previously reported in this preparation. 3. A raised superfusate [K+] also induced a Ca2+ transient, due to transmembrane influx of Ca2+. This transient was depressed by extracellular acidosis, but unaffected by changes to pHi. The L-type Ca2+ current was similarly affected by changes to pHo, but not by alteration of pHi. 4. The results suggest that extracellular acidosis depresses the Ca2+ transient by reducing transmembrane influx through the L-type Ca2+ channel. The increase in the carbachol- and caffeine-induced Ca2+ transients by intracellular acidosis is due to enhancement of Ca2+ uptake into intracellular stores as a result of a raised resting [Ca2+]i.