THE ACTIONS OF EXTRACELLULAR H+ ON THE ELECTROPHYSIOLOGICAL PROPERTIES OF ISOLATED HUMAN DETRUSOR SMOOTH-MUSCLE CELLS

1. The influence of extracellular pH changes on intracellular pH and [Ca2+], as well as on L-type Ca2+ currents, has been investigated in isolated human detrusor smooth muscle cells. 2. Alteration of extracellular pH by changing superfusate P-CO2 also changed intracellular pH. A change of superfusate pH made by altering the [NaHCO3] at constant P-CO2 was not reflected in a change in intracellular pH. 3. Extracellular acidosis attenuated the magnitude and rate of change of intracellular [Ca2+] evoked by raising the extracellular [KCl]. 4. Extracellular acidosis attenuated the rate of rise and amplitude of the action potential, as well as the magnitude of the L-type Ca2+ current. In the pH range 6.78-7.62 no alteration to the voltage dependence of Ca2+ current activation or inactivation was recorded. 5. A close proportional relationship between tension generated by multicellular strips and the magnitude of peak inward Ca2+ current in isolated cells was noted over a wide range of the two variables using a number of interventions, including alteration to extracellular pH, [Ca2+] and [Mg2+]. 6. Extracellular acidosis attenuated the magnitude of caffeine-dependent intracellular Ca2+ transients and the resting [Ca2+](i) between transients. Acidosis was without effect on the rise of [Ca2+](i) induced by carbachol. 7. The results suggest that the negative inotropic effect of extracellular acidosis can be accounted for by attenuation of the L-type Ca2+ current. The results also imply that intracellular stores are influenced by transmembrane Ca2+ fluxes at rest and that such fluxes are also attenuated by extracellular H+