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 (ICa), transient outward potassium current (ITO), and inwardly rectifying potassium current (IK1) are involved in the prolongation of the early (ICa, ITO) and late (IK1) 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 ICa among age groups once currents were normalised for capacitative surface area. The voltage dependence of ICa 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 < or = 0.05) slowing in the time course of inactivation of ICa; 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 ICa inactivation were observed. There was an age associated decrease in peak ITO 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 ITO 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 (tau 2) component.

Conclusions: ICa density is maintained in senescence; ICa inactivation, however, is slowed. Age related differences in action potential duration and ICa inactivation were reduced by buffering intracellular Ca2+. ITO 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.