An investigation into the mechanism whereby pH affects tension in guinea-pig ureteric smooth muscle.

1. We have altered intracellular (pHi) and extracellular pH (pHo) in the smooth muscle of guinea-pig ureter and determined the effects on evoked phasic contractions. In order to investigate the mechanisms underlying the effects of pH alteration, intracellular Ca2+ ([Ca2+]i), pHi, electrical activity and force were measured. 2. Intracellular acidification, produced by the weak acid butyrate, application of CO2 at constant pHo or removal of weak bases, greatly increased phasic contractions. Alkalinization with weak bases or by removal of CO2 inhibited contractions. The results were similar whether Hepes or CO2-HCO3-buffered the solutions. 3. Phasic contractions were preceded by intracellular Ca2+ transients in the ureter. Acidification of the cytoplasm led to an increase in the amplitude of the Ca2+ transient, and alkalinization decreased its magnitude. 4. In the ureter the action potential leads to Ca2+ influx, therefore electrophysiological recordings of its configuration were made during alteration of pHi. Acidification led to the action potential duration and amplitude being increased, whereas alkalinization shortened the action potential and reduced its amplitude. 5. As the effects of acidification on the action potential resembled the effects of blocking of K+ channels, we investigated whether pHi alteration was able to alter tension when K+ channels were blocked by tetraethylammonium. Acidification was unable to potentiate force under these conditions nor did alkalinization decrease force. 6. External pH over the range 6.8-8.0 had little or no effect on pHi, phasic contractions and [Ca2+]i. Tonic contractions were enhanced, however, when pHo was increased. 7. These data suggest that pHi alteration in the guinea-pig ureter modulates the action potential, probably by alteration of K+ currents. Subsequent changes in [Ca2+]i and contraction then occur. A potentiating effect of acidic pH on force is not common in muscle, but may be a characteristic of the smooth muscle of the urinary tract. Changes of pHo had little effect on phasic force or pHi, but modulated tonic contractions. The possible physiological significance of these results is discussed.