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 Ca + 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 [Ca ]i and SR Ca + content. Results: Ca -dependent, steady state INa/Ca density was increased in hypertrophied myocytes (P< 0.05). Ca 2 + release from the SR was also increased, whereas resting [Ca ]i and the rate of decline of [Ca 2 ]i to control levels were unchanged. SR Ca 2 + 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 Ca + transients or INa/Ca was not significantly different between control and hypertrophied myocytes. Ca 2 -dependence of INa/Ca, examined by comparing the slope of the descending phase of the hysteresis plots of INa/Ca vs. [Ca 2 ]i, was also similar in the two groups of cells. Conclusion: Data show that SR Ca + release and SR Ca + 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 Ca + homeostasis in hypertrophied cardiac muscle, possibly through increased reverse Na/Ca + exchange, particularly at low stimulation frequencies. D 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.