Diminished Na+/K+ and Ca2+ pump activities in the Ca2+ depleted heart: possible role in the development of Ca2+ overload during the Ca2+ paradox.
Experiments were carried out to test the hypothesis that membrane injury associated with Ca2+ depletion of the heart is involved in the development of Ca2+ overload during the Ca2+ paradox phenomenon. Biochemical properties of sarcolemma (SL) and sarcoplasmic reticulum (SR) isolated from the rabbit heart after 10 min of Ca2+-free perfusion were examined. This treatment predisposes hearts to the Ca2+ paradox as assessed by perfusate creatine kinase (CK) activity and heart contractility during reperfusion with Ca2+. Homogenates prepared from Ca2+ depleted heart were examined for their capacity to accumulate Ca2+ in the presence of ATP, which is mainly a property of the SR Ca2+ pump. The initial rate of Ca2+ pumping was 55% less in the Ca2+ depleted heart. The activities of 5'-nucleotidase, Na+/K+-ATPase and Na+/Ca2+ antiporter, and the Ca2+ permeability were studied in isolated SL vesicles. Na+/K+-ATPase activity was 75% less in SL isolated from Ca2+ depleted hearts, no significant changes were observed with the other parameters studied. Calmodulin (CaM) content in SL, assayed by radioimmunoassay, was unchanged. However, a 98% increase was observed in homogenates prepared from Ca2+ depleted hearts. The possible involvement of CaM in the Ca2+ paradox phenomenon is discussed. The data provide evidence that the net Ca2+ gain of myocardial cells in Ca2+ repletion may in part be associated with a loss of the ability of the SL and SR to remove Ca2+ from the cytosol.
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002147:Calmodulin / Q000032:analysis; D007473:Ion Channels / Q000502:physiology*; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000032:analysis / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D011817:Rabbits; D012508:Sarcolemma / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D012964:Sodium / Q000378:metabolism*
D002147:Calmodulin; D007473:Ion Channels; D012964:Sodium; D011188:Potassium; D002118:Calcium