An endogenous positive inotropic factor (EPIF) from porcine heart: Its effects on sarcoplasmic reticular (SR) Ca2+ metabolism

We have isolated an endogenous positive inotropic factor (EPIF) from porcine left heart ventricular tissue, which demonstrated to have only weak digitalis-like properties including the inhibition of myocardial Na+,K+-ATPase. EPIF completely lacks digitalis-like toxicity such as after-contractions in larger doses. In our recent studies, we have demonstrated that EPIF produces a decrease in the amplitude of the post-rest rapid cooling contracture which indicated that EPIF may release Ca2+from the sarcoplasmic reticulum. In the present study, the effects of EPIF were investigated on the Ca2+uptake and release properties of SR enriched membrane vesicles from rat heart. At pH 6.8 and in the presence of oxalate, EPIF dose-dependently inhibited the ATPdependent uptake of Ca2+by SR vesicles. Concentrations as low as 25 ul (in 1 mL uptake medium) of EPIF caused a 45-47% reduction in the uptake of Ca2+within 3-4 min. Increases in EPIF concentration to 50 ul/mL caused additional reduction of only 15-20% in the uptake of Ca2+. Concentrations of 25 ul/mL of EPIF had little or no effects on passive release of actively loaded Ca2+in SR vesicles. On doubling the concentrations to 50 ul/mL EPIF, however, enhanced the release of Ca2+by 25-28% during 1-2 min. and 44-48% after 4 min of incubation of Ca2+loaded vesicles in the release medium. Relatively smaller effects of EPIF on Ca2+release implies that EPIF may mainly lower the uptake of Ca2+in SR. This reduced uptake of Ca2+may be explained by the EPIF-induced inhibition of Ca2+pump.