Na+/Ca2+ exchange current INa/Ca) and sarcoplasmic reticulum (SR) Ca2+ release in catecholamine-induced cardiac hypertrophy.

Abstract

Catecholamines that accompany acute physiological stress are also involved in mediating the development of hypertrophy and failure. However, the cellular mechanisms involved in catecholamine-induced cardiac hypertrophy, particularly Ca2+ handling, are largely unknown. We therefore investigated the effects of cardiac hypertrophy, produced by isoprenaline, on INa/Ca and sarcoplasmic reticulum (SR) function in isolated myocytes. Methods: INa/Ca was studied in myocytes from Wistar rats, using descending (+80 to ¿110 mV) voltage ramps under steady state conditions. Myocytes were also loaded with fura-2 and either field stimulated or voltage clamped to assess [Ca2+]i and SR Ca2+ content. Results: Ca2+-dependent, steady state INa/Ca density was increased in hypertrophied myocytes (P<0.05). Ca2+ release from the SR was also increased, whereas resting [Ca2+]i and the rate of decline of [Ca2+]i to control levels were unchanged. SR Ca2+ content, estimated by using 10.0 mmol/l caffeine, was also significantly increased in hypertrophied myocytes, but only when myocytes were held and stimulated from their normal resting potential (¿80 mV) but not from ¿40 mV. However, the rate of decline of caffeine-induced Ca2+ transients or INa/Ca was not significantly different between control and hypertrophied myocytes. Ca2+-dependence of INa/Ca, examined by comparing the slope of the descending phase of the hysteresis plots of INa/Ca vs. [Ca2+]i, was also similar in the two groups of cells. Conclusion: Data show that SR Ca2+ release and SR Ca2+ content were increased in hypertrophied myocytes, despite an increase in the steady state INa/Ca density. The observation that increased SR function occurred only when myocytes were stimulated from ¿80 mV suggests that Na+ influx may play a role in altering Ca2+ homeostasis in hypertrophied cardiac muscle, possibly through increased reverse Na+/Ca2+ exchange, particularly at low stimulation frequencies.