Calcium reintroduction decreases viability of cardiac myocytes from copper-deficient rats

Copper deficiency leads to profound cardiac hypertrophy and failure. Myocyt es were isolated from hearts of copper-deficient and copper-adequate male H oltzman 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 (copp er-adequate) rats drank water supplemented with cupric sulfate (20 mg Cu/L) , Compared with copper-adequate rats, copper-deficient rats had lower hemat ocrits, liver copper concentrations and plasma ceruloplasmin activities, an d higher heart weights and liver iron concentrations. When myocytes were is olated in low calcium media (1 mu mol/L), cell viability was not affected b y diet history. However, upon restoration to more physiologic levels of cal cium (1 mmol/L), cells from copper-deficient rats were less viable, exhibit ing an average loss of 34 and 40% in Experiments 1 and 2, respectively, com pared with a 9.5 and 13% loss of cells, respectively, from the copper-adequ ate 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 ano ther model of cardiac hypertrophy, the calcium sensitivity of myocytes from hypertrophic hearts of Sprague-Dawley rats with aortic constrictions was f ound not to differ from that of sham-operated rats. Thus, cardiac hypertrop hy associated with postnatal copper deficiency results in a unique increase d calcium intolerance of isolated myocytes.