The effects of changing intracellular pH on calcium and potassium currents in smooth muscle cells from the guinea-pig ureter

 Guinea-pig ureteric smooth muscle is unusual in that intracellular acidification increases and alkalinization decreases force production. To help elucidate the mechanism underlying these effects on force we have investigated the effects of changing intracellular pH on both calcium and potassium currents in single cells isolated from the guinea-pig ureter to determine their possible role in force development. Depolarization to +40 mV resulted in a fast transient outward current which was inhibited by 4-aminopyridine but not tetraethylammonium. Intracellular alkalinization (20 mM trimethylamine) increased this current to 179 ± 24% of the control and resulted in the development of a slowly activating large outward current which was inhibited by tetraethylammonium and washout. Acidification (40 mM sodium butyrate) decreased the fast transient outward current to 58 ± 3% of the control and did not produce a slowly activating current. When potassium was replaced by caesium in the pipette solution, depolarization to 0 mV resulted in an inward calcium current which was abolished by nifedipine. Intracellular alkalinization increased this current to 126 ± 11% of the control whereas acidification had the opposite effect, decreasing it to 55 ± 10%. Furthermore, current-clamp experiments showed that intracellular alkalinization inhibited the amplitude of the action potential, therefore decreasing excitability of the cell. From our results, we suggest that the predominant effects of intracellular pH on force production in the guinea-pig ureter are mediated via the modulation of outward potassium currents (thereby reducing excitability of the tissue) rather than the effects on the inward calcium current.