Calcium reintroduction decreases viability of cardiac myocytes from copper-deficient rats.
Copper deficiency leads to profound cardiac hypertrophy and failure. Myocytes were isolated from hearts of copper-deficient and copper-adequate male Holtzman rats to characterize size and function of the cells. Weanling rats were offered a semipurified diet low in copper in two separate experiments (Experiment 1, 0.45 mg Cu/kg and Experiment 2, 0.30 mg Cu/kg). Control (copper-adequate) rats drank water supplemented with cupric sulfate (20 mg Cu/L). Compared with copper-adequate rats, copper-deficient rats had lower hematocrits, liver copper concentrations and plasma ceruloplasmin activities, and higher heart weights and liver iron concentrations. When myocytes were isolated in low calcium media (1 micromol/L), cell viability was not affected by diet history. However, upon restoration to more physiologic levels of calcium (1 mmol/L), cells from copper-deficient rats were less viable, exhibiting an average loss of 34 and 40% in Experiments 1 and 2, respectively, compared with a 9.5 and 13% loss of cells, respectively, from the copper-adequate rats. Addition of the calcium channel blocker, verapamil, did not block this calcium-dependent loss of viability nor did the mitochondrial calcium channel blockers, ruthenium red and cyclosporin A. For comparison with another model of cardiac hypertrophy, the calcium sensitivity of myocytes from hypertrophic hearts of Sprague-Dawley rats with aortic constrictions was found not to differ from that of sham-operated rats. Thus, cardiac hypertrophy associated with postnatal copper deficiency results in a unique increased calcium intolerance of isolated myocytes.
Prohaska
J R
JR
Department of Biochemistry School of Medicine, University of Minnesota, Duluth, MN 55812, USA.
Heller
L J
LJ
D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000008:administration & dosage / Q000494:pharmacology*; D006332:Cardiomegaly / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002570:Ceruloplasmin / Q000378:metabolism; D003300:Copper / Q000008:administration & dosage / Q000172:deficiency* / Q000494:pharmacology; D004032:Diet; D006321:Heart / Q000187:drug effects*; D008099:Liver / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley
D003300:Copper; D002570:Ceruloplasmin; D002118:Calcium