THE INTERCONNECTION BETWEEN ACTIVE TRANSPORT AND CONTRACTURE IN UTERINE TISSUES

Abstract

A study of the effects of several procedures known to interfere with active transport in rat, rabbit, and cat uterine muscle has revealed certain differences between muscles and between inhibitory procedures. Ouabain, fluoride, and sudden cooling caused an initial contracture followed by subsequent loss of contractility in circumstances in which they inhibit active transport. Removal of external potassium increased and subsequently decreased isometric contractions at 37 °C of rat and cat uterine segments, and in most of rat uterine horns caused contracture at 24 °C followed by relaxation and loss of contractility. The parallelism between the initial contracture and inhibition of active transport extends to the necessity for a concentration of 10−4 M to 10−3 M ouabain for initiation of both in rat uteri in contrast to the effectiveness of 10−7 M to 10−5 M in rabbit and cat uteri. The contracture induced by ouabain in rat uteri was potentiated by a decrease in external potassium and prevented by an increase. Removal of the glucose from the medium for 1 to 2 minutes potentiated both ouabain and potassium depletion contractures, but did not significantly increase potassium loss. Lower concentrations of NaF caused contracture in the absence of glucose. The contractures induced by NaF and by cold were obtained in uteri depolarized by K2SO4 Ringer solution and none were prevented by selective antagonists to acetylcholine, adrenaline, histamine, or serotonin. All the procedures producing contracture were ineffective in uteri depleted of calcium. All are known to interfere with the activity of the Mg- and Na + K-activated membrane ATPase believed to be involved in active transport. Therefore, it is proposed that inhibition of this enzyme in uteri causes contracture. In view of other work, this is presumed to occur by failure of active extrusion or failure of binding of calcium at the cell surface leading to a net calcium influx. The potentiation of contractures by removal of glucose occurs too rapidly to derive from glucose or glycogen depletion and is attributed to interaction between glucose transport and cation transport mechanisms.In contrast to ouabain, fluoride, potassium depletion, and cold, iodoacetate and dinitrophenol inhibit active transport and contractility in uterine muscle without causing an initial contracture. It is proposed that these substances act either by decreasing energy supply or by acting at a non-membrane site different from that at which substances causing contracture act. Cyanide was less effective as an inhibitor of either process, and oxidative metabolism is presumed not to be essential for energy supply in these tissues. In general, the loss of ability of uterine muscle to contract on chemical stimulation was directly related to the extent of potassium depletion. Both potassium depletion and loss of contractility were attributed to decreased energy supply.Ouabain in concentrations insufficient to cause contracture or potassium loss in rat uteri prevented rhythmic activity.