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.
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Institute of Urology & Nephrology, University College London, 67 Riding House Street, London W1P 7PN, UK.
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D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002245:Carbon Dioxide / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005110:Extracellular Space / Q000502:physiology; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000502:physiology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010313:Partial Pressure; D011188:Potassium / Q000494:pharmacology; D017693:Sodium Bicarbonate / Q000494:pharmacology; D013997:Time Factors; D001743:Urinary Bladder / Q000502:physiology
D002245:Carbon Dioxide; D002110:Caffeine; D001285:Atropine; D017693:Sodium Bicarbonate; D002217:Carbachol; D011188:Potassium; D002118:Calcium