EFFECTS OF METABOLIC INHIBITION AND CHANGES OF INTRACELLULAR PH ON POTASSIUM PERMEABILITY AND CONTRACTION OF RAT UTERUS

1. We have investigated the role of changes of potassium efflux in the inhibition of uterine force produced by cyanide. K+ efflux (Rb-86) wa s measured from pregnant and non-pregnant rat myometrial strips during metabolic inhibition with cyanide and following manoeuvres to displac e intracellular pH (pH(i)). 2. Cyanide greatly reduced or abolished sp ontaneous contractions. If the membrane was depolarized directly at th is stage (by elevating external K+) then contraction redeveloped. This suggests that the initial depression of force is due to a failure of membrane excitation. 3. Cyanide reversibly increased Rb-86 efflux (30- 35%) in both pregnant and non-pregnant uteri and contraction was reduc ed. The increase in Rb-86 efflux with cyanide was not secondary to cha nges of membrane potential as it also occurred in both high-K+ and Ca2 +-free solutions. 4. Glibenclamide (20 mum), an antagonist of K(ATP)channels, reduced the cyanide-evoked increase of Rb-86 efflux by about 50%. The glibenclamide-insensitive component of efflux persisted in a Ca 2+ -free solution. Despite its action on Rb-86 efflux, glibenclami de did not restore contraction. 5. Intracellular pH falls during metab olic inhibition. We therefore investigated whether reducing pH(i) (in the absence of cyanide) had an effect on Rb-86 efflux. Application of the weak acid butyrate (60 mm, at constant external pH, 7.4) had no si gnificant effect on Rb-86 efflux. Thus it is unlikely that the acidifi cation in hypoxia contributes to the increased K+ efflux. 6. Intracell ular alkalinization produced by the weak base trimethylamine (60 mm) i ncreased the frequency of uterine contraction and the Rb-86 efflux. Ho wever, there was no effect on the Rb-86 efflux in a Ca 2+ -free soluti on. The increased efflux is therefore presumably a consequence of the increased frequency. 7. It is concluded that metabolic inhibition prod uced by cyanide, produces an increase in K+ efflux from the myometrium . Part of this efflux is glibenclamide sensitive. This increased K+ ef flux will lead to hyperpolarization of the myometrial membrane and thu s decrease excitation. Thus reduced surface membrane excitability will contribute to the fall of force in hypoxia; specifically it may cause the initial loss of spontaneous contractions in the uterus.