Age associated changes in membrane currents in rat ventricular myocytes

Objective: Action potential duration of senescent rat ventricular myocytes is longer than in young adults. The aim of the study was to determine whether age related changes in L-type calcium current (I_Ca), transient outward potassium current (I_TO), and inwardly rectifying potassium current (I_KI) are involved in the prolongation of the early (I_Ca, I_TO) and late (I_KI) portions of the rat action potential plateau. Methods: Whole cell voltage clamp techniques were used to study these currents in ventricular myocytes isolated from young (2-3 months), middle aged (8-9 months), and senescent (24-25 months) rats. Results: There were no differences in the magnitude of I_Ca among age groups once currents were normalised for capacitative surface area. The voltage dependence of I_Ca activation and steady state inactivation in the three age groups was also similar. At test potentials of 0 and +10 mV, there was a significant (p ≤s 0.05) slowing in the time course of inactivation of I_Ca; the time constants of inactivation increased with age [young v old in ms(SEM): 0 mV, 22.2(2.2) v 38.0(5.0) (slow); +10 mV, 8.0(2.0) v 15.6(2.0) (fast)]. With internal EGTA to buffer intracellular Ca²⁺, no significant age related differences in action potential duration or the time course of I_Ca inactivation were observed. There was an age associated decrease in peak I_TO density in the old (n = 25) compared to the young (n = 25) cell group (p<0.05). The only age associated change in the kinetic properties of I_TO was a small but consistent slowing in the time constants of inactivation at most test voltages measured, with significance occurring at 0 mV in the slow (τ₂) component. Conclusions: I_Ca density is maintained in senescence; I_Ca inactivation, however, is slowed. Age related differences in action potential duration and I_Ca inactivation were reduced by buffering intracellular Ca²⁺. I_TO channels appear to retain normal function through the aging process but overall there is a reduced channel density. The age associated changes in these currents should contribute to prolongation of action potential duration of the early plateau phase seen in the senescent rat.