Temperature-dependent development of ouabain action in isolated guinea pig heart: Differences in sodium influx?

Abstract

At 30°C the development of the positive inotropic action of 0.3 μM ouabain observed in isolated left atrial muscle preparations of guinea-pig heart was significantly slower and more dependent on the frequency of electrical stimulation than it was at 37°C. The hypothesis was tested that such differences are due to a variation in the rate of leak sodium influx, and ensuing differences in glycoside binding to sarcolemmal Na,K-ATPase. Monensin or grayanotoxin, agents which have been shown to increase sodium influx, caused faster development of the inotropic action of ouabain at 30°C when muscle preparations were stimulated at 0.5 or 1 Hz but their effect was smaller at 2 or 3 Hz stimulation. The contracture caused by toxic concentrations of ouabain in quiescent preparations developed faster at the higher temperature. Ouabain binding to sarcolemmal Na,K-ATPase which occured during exposure of atrial muscle preparations to the glycoside at 25°C for 30 min was less than the corresponding value observed after a similar exposure at 37°C; however, electrical stimulation increased glycoside binding to a greater extent at the lower temperature. The ouabain-sensitive 42K + uptake was lower in quiescent preparations at 30°C than at 37°C. Moreover, the enhancement of the ouabain-sensitive 42K + uptake caused by electrical stimulation was greater at 30°C than at 37°C. These results are consistent with the hypothesis that, at lower temperatures, the rate of sodium influx is low and is the factor determining the rate of development of the inotropic action of ouabain. At a higher temperature, a relatively high sodium leak influx seems to make the onset of ouabain action less dependent on the frequency of stimulation.