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 PCO2 also changed intracellular pH. A change of superfusate pH made by altering the [NaHCO3] at constant PCO2 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+.
Department of Physiology, UMDS, London.
C H
CH
Fry
C R
CR
Gallegos
B S
BS
Montgomery
D000138:Acidosis / Q000503:physiopathology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002245:Carbon Dioxide / Q000378:metabolism; D004594:Electrophysiology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation / Q000502:physiology
D015220:Calcium Channels; D002245:Carbon Dioxide; D002217:Carbachol; D011188:Potassium; D002118:Calcium