title: Effects of metabolic inhibition and changes of intracellular pH on potassium permeability and contraction of rat uterus.
abstract: 1. 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 Ca(2+)-free solutions. 4. Glibenclamide (20 microM), an antagonist of K+ATP channels, reduced the cyanide-evoked increase of 86Rb efflux by about 50%. The glibenclamide-insensitive component of efflux persisted in a Ca(2+)-free solution. Despite its action on 86Rb efflux, glibenclamide did not restore contraction. 5. Intracellular pH falls during metabolic inhibition. We therefore investigated whether reducing pHi (in the absence of cyanide) had an effect on 86Rb efflux. Application of the weak acid butyrate (60 mM, at constant external pH, 7.4) had no significant effect on 86Rb efflux. Thus it is unlikely that the acidification in hypoxia contributes to the increased K+ efflux. 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 Ca(2+)-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.
authors.affiliation: Physiological Laboratory, University of Liverpool.
authors.forename: R C
authors.initials: RC
authors.lastname: Heaton
authors.forename: S
authors.initials: S
authors.lastname: Wray
authors.forename: D A
authors.initials: DA
authors.lastname: Eisner
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000502:physiology; D003486:Cyanides / Q000494:pharmacology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008744:Methylamines / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012414:Rubidium Radioisotopes; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: D000963:Antimetabolites; D003486:Cyanides; D008744:Methylamines; D015221:Potassium Channels; D012414:Rubidium Radioisotopes; D000255:Adenosine Triphosphate; C023336:trimethylamine; D011188:Potassium; D005905:Glyburide