Hyperpolarization and slowing of the rate of contraction in human uterus in pregnancy by prostaglandins E-2 and F-2 alpha: involvement of the Na+ pump

1. The effects of prostaglandins E-2 (PGE) and F-2 alpha (PGF) on membrane potential and isometric tension and cytoplasmic free calcium concentration ([Ca2+](i)) and tension were studied in strips of uterine smooth muscle obt ained from women undergoing Caesarean delivery at term and during establish ed labour. 2. Prostaglandins (PGs) evoked a biphasic response. The excitatory componen t consisted of depolarization of the membrane, which initiated spike action potentials, an increase in [Ca2+](i) and tension development. The membrane remained depolarized at -19 +/- 1 mV for about 2 min, then repolarized abr uptly, [Ca2+](i) promptly returned to basal levels, and tension development ceased. 3. This component of the response to PGE or PGF was followed by a slow hype rpolarization which reached -85 +/- 2 mV (n = 22) at term and -70 +/- 2 mV (n = 9) during labour, and during which spontaneous action potentials and t ension development did not occur. 4. Nifedipine (10(-6) M) abolished spontaneous activity abolished PG-induce d action potentials and reduced the increase in [Ca2+](i) (9 +/- 3%, n = 6) , the depolarization (10 +/- 1 mV, n = 14), the tension (2 +/- 1 %, n = 14) and the hyperpolarization (9 +/- 1 mV, n = 14, at term). 5. A variety of K+ channel blockers were without effect on the peak amplitu de of the PG-induced hyperpolarization but the latter did not occur in the presence of ouabain (10(-6) M) Or in K+-free or low-Na+ solutions, suggesti ng an involvement-of the Na+-K+-ATPase pump. 6. In conclusion, a substantial dependence on Ca2+ influx through voltage-o perated Ca2+ channels accounts for the importance of membrane potential in regulating contractions in human uterine smooth muscle. The classical excit atory effect of PGE and PGF is followed by hyperpolarization involving the Na+-K+-ATPase pump. The hyperpolarization restricts the response to a singl e contraction and decreases the frequency of subsequent contractions. The a mplitude of the hyperpolarization decreases during labour, allowing contrac tion frequency to increase. Its persistence at this time ensures complete r elaxation between each single robust contraction, preventing spasm of the u terus that would restrict blood flow to the fetus during delivery.