苦参碱与E-4031,多非利特和RP58866对家兔心肌I_(k1)的作用比较(英文)

目的　比较苦参碱与E 4 0 31,多非利特和RP5 886 6对家兔单个心室肌细胞的内向整流钾电流(Ik1)的效价和效能的不同 ,揭示苦参碱抗心律失常作用弱于西药的原因。方法　应用全细胞膜片钳技术记录苦参碱与E 4 0 31,多非利特和RP5 886 6对家兔Ik1的影响。结果　苦参碱 1和 10 μmol·L- 1对家兔Ik1无明显影响。在实验电压为 - 12 0mV和保持电压为 - 70mV ,苦参碱 5 0和 10 0 μmol·L- 1对Ik1分别抑制达 6 % (n =8,P <0 .0 5 )和 8% (n =8,P <0 .0 5 ) ;在实验电压为 - 5 0mV ,抑制Ik1达 4 % (n =8,P <0 .0 5 )和 8% (n =8,P <0 .0 5 )。在实验电压为 - 12 0mV ,E 4 0 311和 10 μmol·L- 1使Ik1分别降低10 % (n =6 ,P <0 .0 5 )和 4 5 % (n =6 ,P <0 .0 5 )。在 - 5 0mV ,Ik1分别降低 5 % (n =6 ,P <0 .0 5 )和35 % (n =6 ,P <0 .0 5 )。在实验电压为 - 12 0mV ,多非利特 1和 10 μmol·L- 1使Ik1降低 19% (n =8,P <0 .0 5 )及 2 5 % (n =8,P <0 .0 5 )。在 - 5 0mV ,Ik1分别降低 11%和 19% (n =8,P <0 .0 5 )。在实验电压为 - 12 0mV ,RP5 886 6 1和 10 μmol·L- 1使Ik1分别降低 2 1% (n =8,P <0 .0 5 )和 5 0 % (n =8,P <0 .0 5 )。在 - 5 0mV ,Ik1分别降低 6 % (n =8,P <0 .0 5 )和11% (n =8,P <0 .0 5

Inhibitory effects of matrine, E-4031, dofetilide and RP58866 on inward rectifier potassium current in rabbit ventricular myocytes

AIM To explore the cause of the weaker antiarrhythmic effects of matrine than that of E-4031, dofetilide and RP58866. METHODS Whole-cell patch-clamp technique was used to record ionic currents in rabbit ventricular myocytes. RESULTS 1 and 10 μmol·L-1 matrine did not affect the inward rectifier potassium current (Ik1). 50 and 100 μmol·L-1 matrine reduced Ik1 by 6% (n=8, P<0.05) and 8% (n=8, P<0.05), respectively at test potential of -120 mV from holding potential of -70 mV. At -50 mV, Ik1 decreased by 4% (n=8, P<0.05) and 8% (n=8, P<0.05). E-4031, dofetilide and RP58866 significantly inhibited Ik1. At test potential of -120 mV, 1 and 10 μmol·L-1 E-4031 decreased Ik1 by 10% (n=6, P<0.05) and 45% (n=6, P<0.05). At -50 mV, Ik1 was decreased by 5% (n=8, P<0.05) and 35% (n=8, P<0.05), respectively. 1 and 10 μmol·L-1 dofetilide decreased Ik1 by 19% (n=6, P<0.05) and 25% at -120 mV. At -50 mV, Ik1 was decreased by 11% (n=6, P<0.05) and 19% (n=6, P<0.05), respectively. At -120 mV, 1 μmol·L-1 and 10 μmol·L-1 RP58866 decreased Ik1 by 21% (n=8, P<0.05) and 50% (n=8, P<0.05). At -50 mV, Ik1 was decreased by 6% (n=8, P<0.05) and 11% (n=8, P<0.05), respectively. CONCLUSION The lower efficacy and potency of matrine in the inhibitory effects on Ik1 than that of E-4031, dofetilide and RP58866 is one of the reasons for weaker antiarrhythmic effects of the Chinese herb than that of pure compounds.