Suppression of cellular injury during the calcium paradox in rat heart by factors which reduce calcium uptake by mitochondria.
Isolated Langendorff perfused rat hearts were used to study changes in the Ca, Na and K content, contractile force and the loss of cellular material during the Ca paradox. Five minutes perfusion with Ca-free solution containing 1 mM EGTA, followed by 10 min of reperfusion in 1.8 mM Ca causes irreversible contracture, K loss, increase in Na and Ca and a massive release of myoglobin and other cellular material into the perfusate (the calcium paradox). During the Ca-free perfusion the ventricles gain Na but the K content decreases slightly. The size of the Na gain appears to depend upon the buffer used and is larger in bicarbonate than in Tris. When HCO3- or H2PO4- ions are omitted from the bathing solution (in Tris, HEPES, or TES buffered salines) the adverse effects of Ca readmission are reduced. Tris buffer gives the best protection. Metabolic inhibition with FCCP (5 X 10(-7) M), or with CN-(2 X 10(-3) M) together with iodoacetic acid (2 X 10(-3) M), decreases Ca uptake during the Ca paradox and inhibits the release of cellular material. In both cases a contracture is observed. Ruthenium red (10(-4) M) does not inhibit the Ca readmission contracture but reduces the release of cellular material and the gain of Ca and Na. The results suggest that the loss of cellular constituents during the calcium paradox, is related to an active uptake of Ca by the mitochondria and may lead to massive changes in the cellular ion concentration, during Ca-repletion.
D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002021:Buffers; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D009202:Cardiomyopathies / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D010710:Phosphates / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001639:Bicarbonates; D002021:Buffers; D010710:Phosphates; D002118:Calcium