Effects of metabolic inhibition and changes of intracellular pH on potassium permeability and contraction of rat uterus.

Abstract

SUMMARY1. We have investigated the role of changes of potassium efflux in the inhibition of uterine force produced by cyanide. K+ efflux (86Rb) was measured from pregnant and non-pregnant rat myometrial strips during metabolic inhibition with cyanide and following manoeuvres to displace intracellular pH (pHi).2. Cyanide greatly reduced or abolished spontaneous contractions. If the membrane was depolarized directly at this 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 86Rb efflux (30-35%) in both pregnant and nonpregnant uteri and contraction was reduced. The increase in 86Rb efflux with cyanide was not secondary to changes of membrane potential as it also occurred in both high-K+ and Ca2+-free solutions. 6. Intracellular alkalinization produced by the weak base trimethylamine (60 mM) increased the frequency of uterine contraction and the 86Rb efflux. However, there was no effect on the 86Rb efflux in a Ca2+-free solution. The increased efflux is therefore presumably a consequence of the increased frequency.7. It is concluded that metabolic inhibition produced by cyanide, produces an increase in K+ efflux from the myometrium. Part of this efflux is glibenclamide sensitive. This increased K+ efflux will lead to hyperpolarization of the myometrial membrane and thus 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.MS 1322

Consequences of metabolic inhibition in smooth muscle isolated from guinea‐pig stomach

“…This suggests that impairment of spontaneous activity is not mainly due to the activation of ATP-sensitive K¤ channels. This interpretation can be compared with the report in rat uterus that glibenclamide does not restore spontaneous contraction during application of CN (Heaton, Wray & Eisner, 1993), although in that particular smooth muscle the CN-induced increase in ÌÉRb¤ efflux is partially suppressed by glibenclamide (suggesting some activation of ATP-sensitive K¤ channels under exposure to CN). During application of IAA the ã-and á-ATP peaks as well as the â-ATP peak, from which the concentration of ATP is estimated, decreased by similar degrees (Fig.…”

Inhibitory effect of visfatin and leptin on human and rat myometrial contractility

“…As nicotinamide phosphoribosyltransferase catalyses the rate-limiting step in the production of NAD+ from nicotinamide, which is essential when the cellular NAD + pool becomes depleted, then a metabolic role in supporting uterine contractions could be possible under conditions of stress or hypoxia. Uterine contractions are associated with transient hypoxia [47,48] and hypoxia decreases contractile strength [5,49]. Hypoxia has been shown to also stimulate visfatin expression, although to date this does not appear to have been demonstrated on native adipocytes [50,51].…”

Stimulus-dependent modulation of smooth muscle intracellular calcium and force by altered intracellular pH

“…This could be via a direct effect on the Ca t channels or it may be an indirect effect, such as membrane hyperpolarization. There is evidence from 86Rb efflux studies that reduced pHi does not affect K + conductance and therefore might not be expected to reduce membrane excitability [11], consistent with our recent study of isolated uterine cells, which indicated that outward K + currents were not modulated by pH ; change [24]. However there have been no direct measurements of myometrial membrane potential during alteration of pH; and it remains to be established how pH ; -induced changes of force may be related to a pH ; -evoked modulation of the whole pattern of electrical activity.…”