Induction of prolonged excitability in myometrium of pregnant guinea-pigs by prostaglandin F2 alpha.

1. Electrical and mechanical responses to prostaglandin F2 alpha (PGF) were studied in circular myometrium, with or without endometrium, during the first 3 weeks of gestation of the guinea-pig. 2. Muscle strips from which endometrium had been removed became inexcitable within 30-40 min of isolation from the animal such that action potentials and contraction could not be initiated by depolarizing current steps. Raising the concentration of potassium in the perfusing solution resulted in a small contraction. 3. In these preparations PGF induced complex action potentials that consisted of spikes and a prolonged plateau of depolarization. Each action potential was associated with a large phasic contraction. 4. Contractions induced by PGF are unlikely to result predominantly from release of calcium from intracellular stores since the ability of the agonist to evoke a response was reduced by some 97% in the absence of external calcium or in the presence of calcium channel blockers. 5. When preceded by a brief exposure to PGF, the contractile response to high potassium was enhanced to equal that in response to PGF. Enhancement persisted for approximately 30 min after removal of PGF and was not dependent upon the presence of external calcium. 6. Muscle strips with intact endometrium contracted spontaneously for hours. Each contraction was associated with a complex action potential, both of which were abolished by indomethacin. 7. It is concluded that PGF transforms inexcitable calcium channels in the membrane of the smooth muscle cells of the circular myometrium into excitable ones. The study also suggests that endogenous prostaglandin of endometrial origin may prevent the 'run-down' of channels in vivo.