Age-associated alterations in calcium current and its modulation in cardiac myocytes

The calcium current is one of the most important components in cardiac excitation-contraction coupling. During aging, the magnitude of L-type Ca++ channel current (I-Ca,I-L) is significantly increased in parallel with the enlargement of cardiac myocytes, resulting in unaltered I-Ca,I-L density. Since the inactivation of I-Ca,I-L is slowed and the action potential duration is prolonged, the net Ca++ influx during each action potential is likely to be increased in senescent hearts relative to young ones. This augmentation of Ca++ influx may be important for the preserved cardiac function of the older heart in the basal state. However, it increases the risk of Ca++ overload and Ca++-dependent arrhythmias in the senescent heart. During stress, the response of I-Ca,I-L to beta-adrenergic receptor stimulation is markedly reduced, which may be an important cause of the age-related decrease in cardiac reserve function. These age-dependent changes in I-Ca,I-L and its modulations are similar to those observed in the enlarged myocytes of the hypertrophied and failing heart.