The effect of hypercholesterolemia on the sodium inward currents in cardiac myocyte

To determine whether chronic hypercholesterolemia affects sodium inward currents in cardiac myocytes, whole-cell clamp recordings were made in single cardiac myocytes isolated from normo- and hypercholesterolemic rabbits. Modification of the serum cholesterol was accomplished by feeding ten 3-month-old male New Zealand white rabbits with control diet (group I) and ten with 0.5% cholesterol-enriched diet (group II), for 3 months. The serum cholesterol levels of group II were much higher than those of group I (2042 +/- 231 v 82 +/- 9 mg/dl, P < 0.001). The cholesterol-ester and free cholesterol component of cardiac sarcolemma of group II were also significantly higher than those of group I (26.6 +/- 12.4 v 10.8 +/- 4.5 nmole/dl, P < 0.001, and 50.9 +/- 14.8 v 27.5 +/- 6.2 nmole/dl, P < 0.001, respectively). The cell capacitance of hyperlipidemic myocytes seemed larger than that of normolipidemic ones (157.4 +/- 6.4 pF v 103.6 +/- 3.0 pF, P < 0.05). However, the sodium current density on hypercholesterolemic ventricular sarcolemma was significantly lower than that of normolipidemic sarcolemma. This effect was associated with a leftward shift in the inactivation potential and a slowing of the time course of recovery. In conclusion, hypercholesterolemia has important effects on the sodium inward currents in ventricular myocytes, which may be due to a decrease in current density and an alteration in channel functional state.