[Effects of bupivacaine on Na+ and Ca2+ currents in single canine ventricular cells].
The effects of bupivacaine on Na+ and Ca2+ currents in single canine isolated left ventricular cells were examined using whole-cell voltage clamp technique to reveal the mechanism of its negative inotropism. The cells were isolated by enzymatic dispersion and superfused in an oxygenated Tyrode's solution. Bupivacaine 10(-6) M decreased the amplitude of INa and delayed the peak time. These effects were dose and frequency dependent. At a concentration of 10(-3) M, bupivacaine abolished INa. Meanwhile, bupivacaine did not modify ICa at a concentration of 10(-6) M. At 10(-5) M bupivacaine, the amplitude of ICa was depressed by 22% and the depression was dose dependent. These results suggest that low concentration (10(-6) M) of bupivacaine depresses contraction, by reducing intracellular Ca2+ secondary to reduction in intracellular Na+ activity and the Na+-Ca2+ exchange mechanism. At higher concentrations, the reduction in contraction caused by bupivacaine may result partly from a reduced influx of Ca2+.
Shibuya
N
N
Department of Anesthesiology, Faculty of Medicine, Toyama Medical and Pharmaceutical University.
Hatakeyama
N
N
Yamazaki
M
M
Masuda
A
A
Satone
T
T
Ito
Y
Y
Momose
Y
Y
D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D002478:Cells, Cultured; D003864:Depression, Chemical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects*
D015220:Calcium Channels; D015222:Sodium Channels; D002045:Bupivacaine