Contractions of rat uterine smooth muscle induced by acetylcholine and angiotensin II in Ca2+‐free medium

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Abstract
1 The effects of acetylcholine (ACh, 10−4m) and angiotensin II (Ang II, 10−6 M) have been studied on the mechanical and electrical activities of rat myometrial strips perfused in Ca2+-free EGTA-containing solutions. 2 Both ACh and Ang II produced transient contractions, the amplitude of which can be taken as a measurement of the amount of Ca2+ present in a drug-sensitive Ca2+ store. The degree of filling of this store depended on the external Ca2+ concentration, and on the presence of contractile responses during the Ca2+ loading period. The existence of two pathways (either direct or transcytoplasmic) is suggested for Ca2+ uptake into the internal Ca2+ store. 3 The rate of filling of the Ca2+ store in 2.1 mm-Ca2+-containing solution was faster (time to half-maximal response, t1/2 = 29 ± 2.2s, n = 4) than the rate of depletion in Ca2+-free solution (t1/2 = 3 ± 0.3 min, n = 3). The gradual depletion of this store was much slower at 18°C than at 35°C, and in the presence of vanadate which is known to inhibit Ca2+-ATPases. 4 Methoxyverapamil (D600, 10−6-10−5m) had no appreciable effect on the direct Ca2+ uptake or on the release of Ca2+ from the store by ACh and Ang II. Mn2+ (10−3m) completely inhibited the direct pathway to the internal Ca2+ store and also reduced the release of Ca2+. 5 ACh and Ang II induced repetitive depolarizations close to zero potential which did not parallel the transient contractions as a function of the time of perfusion in Ca2+-free solution. Applications of 2 mm EGTA, 135 mm K+ or Ca2+ antagonists which suppressed or reduced the drug-induced depolarizations did not affect appreciably the drug-induced contractions. 6 These results suggest that myometrial cells have an intracellular Ca2+ store sensitive to different stimulus substances. This store is not affected by depolarization of the plasma membrane and is certainly different from that described in voltage-clamp experiments.