The effects of doxorubicin (DOX) on intracellular calcium transients and the cardioprotective effects of a calcium antagonist on DOX-induced impairment of calcium handling were examined in neonatal rat cultured cardiac myocytes. Cultured cardiac myocytes isolated from neonatal Wistar-Kyoto rats were treated with DOX for 24 h. Field-stimulated calcium transients in single myocytes were measured in the presence or absence of isoproterenol using fura-2/AM. Calcium transients were also measured after the addition of DOX to myocytes pretreated with a calcium antagonist, benidipine. DOX reduced the amplitude, maximum velocity of increase and decrease of calcium transients and prolonged the time course of calcium transients and impaired the β- adrenoceptor responsiveness of calcium transients in a concentration- dependent manner. The DOX-induced impairment of calcium transients and β- adrenoceptor responsiveness was improved by 10-8 mol/L of benidipine. However, these improvements decreased with increasing concentrations of benidipine. DOX impaired both the mobilization and removal of intracellular calcium ions in contraction-relaxation cycles and the response of calcium transients to β-adrenoceptor stimulation. Appropriate concentration of benidipine ameliorated DOX-induced impairment of calcium dynamics, suggesting that benidipine, a long-acting calcium antagonist, has potential clinical usefulness on DOX-induced abnormal calcium handling.
CITATION STYLE
Maeda, A., Honda, M., Kuramochi, T., & Takabatake, T. (1999). A calcium antagonist protects against doxorubicin-induced impairment of calcium handling in neonatal in neonatal rat cardiac myocytes. Japanese Circulation Journal, 63(2), 123–129. https://doi.org/10.1253/jcj.63.123
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