Abstract
A comparative study of the effect of calcium load on rat heart mitochondria [RHM(K+)] in which a part of the K+ ions in their matrix were replaced by Na+ ions [RHM(Na+)] was carried out. Calcium loading of RHM(K+) decreased their 2,4-dinitrophenol-uncoupled respiration and reduced the inner membrane potential (∆Ψmito). Swelling of these mitochondria increased in media with 25 mM potassium acetate or 125 mM NH4NO3. These effects of calcium loading were even greater in similar experiments with RHM(Na+). Inhibitors of the mitochondrial permeability transition pore (MPTP), ADP and cyclosporin A (CsA), abolished the above-mentioned effects of Ca2+ completely in experiments with RHM(K+) and only partially in experiments with RHM(Na+). A positive inotropic effect was observed with an increase in the extracellular concentration of Na+, however pre-incubation in a calcium-free solution led to a negative inotropic effect. Thus, the partial replacement of K+ by Na+ in the matrix made rat heart mitochondria more sensitive to Ca2+ and increased the probability of MPTP opening in their inner membrane. Along with an elevation of cytoplasmic [Na+]i, this can further increase calcium overload of cardiomyocytes, making their damage during ischemia/reperfusion more likely.
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