Negative inotropic effects of ATP on the isometric contractions of isolated rat heart muscle.

The effects of ATP on the isometric contractions of isolated rat left ventricular papillary muscle were studied. Exogenously administered ATP had an immediate onset, an abrupt response, progressive recovery and produced dose-related depression in the peak developed tension, maximum rate of tension development and relaxation, which were statistically significant. There were no significant changes in the resting tension, time to peak tension and relaxation time, except for a significantly prolonged relaxation time at the highest concentration of ATP. In the studies of interactions of ATP and either epinephrine or Ca(++), we observed that ATP seemed to interfere with the inotropic effect of epinephrine, while Ca(++) antagonized the negative inotropic action of ATP. We conclude that the site of negative inotropic action of ATP is most likely on the cell membrane, where ATP interferes with Ca(++) flux, and that ATP interferes with the positive inotropic action of epinephrine.