Comparison of aging and hypercholesterolemic effects on the sodium inward currents in cardiac myocytes

To study and to compare the hypercholesterolemic and aging effect on the sodium inward currents (I(Na)) in cardiac myocytes, whole-cell clamp recordings were made in single cardiac myocyte isolated from normo- and diet-induced hypercholesterolemic rabbits of different age groups. The cell capacitance of adult and hyperlipidemic myocytes seemed larger than that of young and normolipidemic ones. However, the sodium current density at a holding potential of -80 mV on adult and hypercholesterolemic ventricular sarcolemma was significantly lower than that on young and normolipidemic one (adult hyperlipidemic: -15.3+/-2.4 pA/pF (n=16), adult control: -28.1+/-3.4 pA/pF (n=13), young hyperlipidemic: -39.5+/-5.4 pA/pF (n=19), young control: -67.3+/-7.8 pA/pF (n=12)). In aging process, this effect was due to a decrease in channel number, a leftward shift in the inactivation potential and a slowing of the time course of recovery. In hypercholesterolemia, however, the major cause was due to the functional change of sodium currents. In addition to decreasing the sodium current magnitude, hypercholesterolemia lowered the threshold for excitation of cardiac myocytes (-50 mV vs -40 mV). In conclusion, aging process depressed the sodium channel activity in ventricular myocytes. In addition to inducing some similar functional alterations of I(Na) as aging process, long-term hypercholesterolemia could also increase the excitability in cardiac myocytes, which was different from aging process.