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.
Wu
C C
CC
Department of Internal Medicine, National Taiwan University College of Medicine, Taipei.
Su
M J
MJ
Chi
J F
JF
Chen
W J
WJ
Hsu
H C
HC
Lee
Y T
YT
D000818:Animals; D006937:Hypercholesterolemia / Q000097:blood / Q000378:metabolism*; D066298:In Vitro Techniques; D017136:Ion Transport; D007700:Kinetics; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D012508:Sarcolemma / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000378:metabolism
D008055:Lipids; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D012964:Sodium