Effects of trimetazidine on the calcium transport and oxidative phosphorylation of isolated rat heart mitochondrial

Trimetazidine (TMZ) added in vitro to isolated cardiac mitochondria at concentrations 10–100 M in the presence of 25–100 nM extramitochondrial Ca²⁺ increased Ca²⁺ uptake and matrix Ca²⁺ concentration. This effect was less evident in the presence of physiologically Na⁺ and Mg²⁺ extramitochondrial concentrations since only 100 M TMZ was able to increase mitochondrial Ca²⁺ entry in the presence of 100 nM Ca²⁺. The drug stimulated a Ca²⁺-cooperative effect on mitochondrial Ca²⁺ transport but did not modify the rate of Ca²⁺ egress stimulated by 10 mM NaCl. An increase in mitochondrial Ca²⁺ level produced by TMZ enhanced oxoglutarate dehydrogenase activity and then ATP synthesis, particularly when 50 nM extramitochondrial Ca²⁺ was used. These data suggest that a possible cardiac mechanism of action of TMZ at mitochondrial level could support ATP synthesis by elevating the mitochondrial Ca²⁺ level.