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

Abstract

The effects of acetylcholine (10(-4) M), prostaglandin E2 (10(-6) M), vanadate (5 X 10(-4) M) and fluoride (10(-2) M) 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. 7 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.