Aging-associated changes in whole cell K+ and L-type Ca2+ currents in rat ventricular myocytes

The effect of aging on cardiac membrane currents remains unclear. This stud y examined the inward rectifier K+ current (I-K1), the transient outward K current (I-to), and the L-type Ca2+ channel current (I-Ca,I-L) in ventricu lar myocytes isolated from young adult (6 mo) and aged (>27 mo) Fischer 344 rats using whole cell patch-clamp techniques. Along with an increase in th e cell size and membrane capacitance, aged myocytes had the same magnitude of peak I-K1 with a greater slope conductance but displayed smaller steady- state I-K1. Aged myocytes also had a greater I-to with an increased rate of activation, but the I-to inactivation kinetics, steady-state inactivation, and responsiveness to L-phenylephrine, an alpha(1)-adrenergic agonist, wer e unaltered. The magnitude of peak I-Ca,I- L in aged myocytes was decreased and accompanied by a slower inactivation, but the I-Ca,I-L steady-state in activation was unaltered. Action potential duration in aged myocytes was pr olonged only at 90% of full repolarization (APD(90)) when compared with the action potential duration of young adult myocytes. Aged myocytes from Long -Evans rats showed similar changes in I-to and I-Ca,I- L but an increased I -K1. These results demonstrate aging-associated changes in action potential , in morphology, and in I-K1, I-to, and I-Ca,I- L of rat ventricular myocyt es that possibly contribute to the decreased cardiac function of aged heart s.