A direct relationship between plasma aldosterone and cardiac L-type Ca2+ current in mice

Aldosterone is involved in a variety of pathophysiological processes that ultimately cause cardiovascular diseases. Despite this, the physiological role of aldosterone in heart function remains elusive. We took advantage of transgenic mouse models characterized by a renal salt-losing (SL) or salt-retaining (SR) phenotype, thus exhibiting chronically high or low plasma aldosterone levels, respectively, to investigate the chronic effects of aldosterone in cardiomyocytes devoid of pathology. On a diet containing normal levels of salt, these animals do not develop any evidence of cardiovascular disease. Using the whole cell patch-clamp technique on freshly isolated adult ventricular cardiomyocytes, we observed that the amplitude of L-type Ca2+ currents (I-Ca) correlates with plasma aldosterone levels. Larger values of I-Ca are associated with high aldosterone concentrations in SL models, whereas smaller values Of I-Ca were observed in the SR model. Neither the time- nor the voltage-dependent properties Of I-Ca varied measurably. In parallel, we determined whether modulation Of I-Ca by blood concentration of aldosterone has a major physiological impact on the excitation-contraction coupling of the cardiomyocytes. Action potential duration, [Ca2+](i) transient amplitude and contraction are increased in the SL model and decreased in the SR model. In conclusion, we demonstrate that the blood concentration of aldosterone exerts chronic regulation Of I-Ca in mouse cardiomyocytes. This regulation has important consequences for excitation-contraction coupling and, potentially, for other Ca2+-regulated functions in cardiornyocytes.