Effect of quinidine on Na-dependent 45Ca transport in isolated adult cardiac cells

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Abstract
The effects of quinidine on Na+-dependent Ca2+ transport in adult rat isolated cardiac cells have been studied by measuring 45Ca2+ uptake and efflux at various external Na+ concentrations ([Na +]o). Quinidine (>50 μM) appreciably inhibited the Ca2+ uptake induced by lowering [Na+]o but had little effect on the Ca2+ efflux. The conclusion that the apparent inhibition of the Na+-dependent Ca2+ uptake was probably due to a general inhibition of the Ca2+ entry through cellular membrane and, at high concentrations, into the intracellular compartments rests on the observations that: (i) in non-steady-state conditions, the fraction of Ca2+ uptake inhibited by quinidine was independent of [Na+]o; (ii) lidocaine, which is known to have effects on membrane electrical activity and Na+ permeability similar to those of quinidine, did not affect the Ca2+ movements; and (iii) when incubated in low [Na+]o, quinidine (>0.2 mM) caused an irreversible contracture of a fraction of the myocyte population, even if about 50% of the Ca2+ uptake induced by lowering [Na+]o was inhibited. The results of this study therefore suggest that quinidine cannot be considered a specific inhibitor of the Na+–Ca2+ exchange in isolated rat cardiac myocytes and indicate the importance of quinidine's effects on intracellular Ca2+ regulation in cardiac muscle.