Intracellular free Ca2+ in the course of the Ca2+ paradox and during poisoning. Ca2+-selective microelectrode measurements in the perfused rat heart.
The free intracellular Ca2+ concentration of perfused rat hearts was measured using Ca2+-selective microelectrodes. In Krebs-Ringer bicarbonate buffer + 0.1 mmol/l Ca2+ (controls) the intracellular Ca2+ concentration was 0.87 +/- 0.07 mumol/l and the membrane potential was -51.5 +/- 0.3 mV. Without glucose the membrane potential approached zero after ca. 60 min, whereas the Ca2+ concentration during 110 min increased only slowly to 10.0 mumol/l. During Ca2+-free perfusion (5 min) both parameters did not change significantly. With reintroduction of 2.0 mmol/l Ca2+ the membrane potential rapidly collapsed and the intracellular Ca2+ concentration was elevated above 0.1 mmol/l within two min. Reperfusion with only 0.1 mmol/l Ca2+ decelerated both changes. Poisoning by carbonyl cyanide-p-trifluoromethoxyphenylhydrazone or antimycin A in Ca2+-free Krebs-Ringer bicarbonate buffer increased the intracellular Ca2+ concentration to 30.0 and 25.0 mumol/l, and the membrane potential was collapsed after 16 and 10 min, respectively. In antimycin A- and Ca2+-containing sucrose medium the intracellular Ca2+ during 16 min increased above 1.0 mmol/l, and the membrane potential began to increase only after 10 min. The results are consistent with the postulate of a hypothetical mechanism of cell injury, in which noxious membrane-cytoskeleton interactions are induced by an elevated intracellular Ca2+ concentration. It is concluded that Ca2+ entry via Na/Ca exchange is not fundamentally involved with induction of injury.
D000818:Animals; D000968:Antimycin A / Q000506:poisoning; D002118:Calcium / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials; D008839:Microelectrodes; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014475:Uncoupling Agents / Q000506:poisoning
D007473:Ion Channels; D014475:Uncoupling Agents; D000968:Antimycin A; D005947:Glucose; D002118:Calcium