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

1 Department of Pharmaceutical Sciences, 2 Department of Pharmacology and Toxicology, and 3 Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205 The effect of aging on cardiac membrane currents remains unclear. This study examined the inward rectifier K + current ( I K1 ), the transient outward K + current ( I to ), and the L-type Ca 2+ channel current ( I Ca,L ) in ventricular 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 the 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 1 -adrenergic agonist, were unaltered. The magnitude of peak I Ca,L in aged myocytes was decreased and accompanied by a slower inactivation, but the I Ca,L steady-state inactivation was unaltered. Action potential duration in aged myocytes was prolonged 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,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,L of rat ventricular myocytes that possibly contribute to the decreased cardiac function of aged hearts. ion channels; action potential; patch clamp