Maintained contractions of rat uterine smooth muscle incubated in a Ca2+‐free solution

Abstract

The effects of acetylcholine (10−4m), prostaglandin E2 (10−6m), vanadate (5 × 10−4m) and fluoride (10−2m) have been studied on the mechanical and electrical activities of rat myometrial strips perfused in Ca2+‐free EGTA‐containing solutions. All four substances produced maintained contractions which could be initiated repeatedly after exposure to Ca2+‐free solution for more than 1 h, without a significant decrease. The largest contractions were obtained with vanadate and the smallest ones with acetylcholine. The tension was usually 7–30% of the control contraction triggered by an action potential in Ca2+ containing solution. Maintained contractions induced by fluoride were unaffected by isoprenaline while those induced by acetylcholine, prostaglandin E2 and vanadate were completely relaxed. Prostaglandin E2 ‐and vanadate‐induced contractions were slightly reduced by Na+ removal or by adding Ca2+ antagonists. In contrast, contractions induced by acetylcholine were suppressed in Na+‐free solution and largely inhibited in the presence of Ca2+ antagonists. The depolarization induced by acetylcholine in Ca2+‐free solution was strongly dependent on the external Na+ concentration. The relationship between the size of the acetylcholine‐induced depolarization and the membrane potential (shifted by constant currents) was linear, giving an apparent reversal potential for acetylcholine close to zero potential. In Ca‐free solutions and in the presence of atropine, Na+ action potentials of long duration can be evoked which produced contractions of the same order of magnitude as those initiated by acetylcholine‐induced depolarizations. These results are consistent with the hypothesis that the maintained contractions in Ca2+‐free solutions induced by several stimulants could be related to Ca2+‐independent mechanisms (fluoride) or Ca2+ release from an intracellular store. This latter mechanism would include both pharmacomechanical (prostaglandin E2, vanadate) and electromechanical (acetylcholine) coupling. 1984 British Pharmacological Society