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 t he sodium inward currents (I-Na) in cardiac myocytes, whole-cell clamp recordings were made in single cardiac myocyte isolated from normo-an d diet-induced hypercholesterolemic rabbits of different age groups. T he cell capacitance of adult and hyperlipidemic myocytes seemed larger than that of young and normolipidemic ones. However, the sodium curre nt density at a holding potential of -80 mV on adult and hypercholeste rolemic ventricular sarcolemma was significantly lower than that on yo ung 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: 3 9.5+/-5.4 pA/pF (n=19), young control: -67.3+/-7.8 pA/pF (n=12)) In ag ing process, this effect was due to a decrease in channel number, a le ftward shift in the inactivation potential and a slowing of the time c ourse of recovery. In hypercholesterolemia, however, the major cause w as due to the functional change of sodium currents. In addition to dec reasing the sodium current magnitude, hypercholesterolemia lowered the threshold for excitation of cardiac myocytes (-50 mV vs -40 mV) In co nclusion, aging process depressed the sodium channel activity in ventr icular myocytes. In addition to inducing some similar functional alter ations of I-Na as aging long-term hypercholesterolemia could also incr ease the excitability in cardiac myocytes, which was different from ag ing process.