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

Objective: 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 I-Na/Ca and sarcoplasmic reticulum (SR) function in isolated myocytes. Methods: I-Na/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 l(Na/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 I-Na/Ca was not significantly different between control and hypertrophied myocytes. Ca2+ -dependence I-Na/Ca, examined by comparing the slope of the descending phase of the hysteresis Plots Of I-Na/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 I-Na/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. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.