人参皂苷Rb1对大鼠心室肌细胞L型钙电流和瞬时外向钾电流的调控作用

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目的研究参松养心胶囊的药物单体—人参皂苷Rb1对大鼠心室肌细胞L型钙电流(Ica,L)和瞬时外向钾电流(Ito)的调控作用。方法 Langendr off灌流装置、胶原酶和蛋白酶混合急性分离大鼠心室肌细胞,用含40μmol/L的人参皂苷Rb1的细胞外液灌流心室肌细胞,每个细胞采用给药前后自身对照,标准的全细胞膜片钳技术记录Ica,L,Ito,所有数据均在细胞破膜后20min内完成,观察人参皂苷Rb1对Ica,L和Ito通道电流的影响。结果 40μmol/L的人参皂苷Rb1对Ica,L和Ito均有抑制作用。在-10mV测试电压下,40μmol/L的人参皂苷Rb1可使Ica,L的最大激活峰值电流密度从(-11.423±-3.125)pA/pF下降至(-5.786±-2.976)pA/pF,抑制率为49.34%±9.78%(n=7,p<0.05),电流密度-电压(I-V)曲线上移,但不改变激活电位、峰电位、反转电位以及曲线的形状;在+60mV测试电压下,40μmol/L的人参皂苷Rb1可使Itof的最大激活峰值电位从35.342±3.126pA/pF下降至26.783±4.153pA/pF,抑制率为24.21%±8.35%(n=8,p<0.05),I-V曲线下移。两通道电流经Boltemann方程拟合的稳态激活曲线给药前后无明显影响,但药物可使稳态失活增快以及失活后恢复减慢(n=7,p<0.05),且人参皂苷Rb1主要抑制Ito的快速电流成分Itof(峰电位),对慢电流成分Itos(维持电位)无明显影响。结论人参皂苷Rb1对Ica,L和Ito通道的电流有显著抑制作用,但不改变Ica,L的通道动力学。 Objective To study the regulation of L-type calcium current (Ica, L) and transient outward potassium current (Ito) in rat ventricular myocytes by ginseng-saponin Rb1. Methods Langendr-perfused device, collagenase and protease were used to separate ventricular myocytes from rats. The ventricular myocytes were perfused with extracellular fluid containing 40μmol / L ginsenoside Rb1. Each cell was treated with its own control before and after administration Cell patch clamp technique was used to record Ica, L and Ito. All the data were recorded within 20min after membrane rupture. The effects of ginsenoside Rb1 on Ica, L and Ito channel currents were observed. Results 40μmol / L of ginsenoside Rb1 had inhibitory effects on Ica, L and Ito. Under the test voltage of -10mV, 40μmol / L of ginsenoside Rb1 decreased the maximum activation peak current density of Ica, L from (-11.423 ± -3.125) pA / pF to (-5.786 ± -2.976) pA / pF, The current density-voltage (IV) curve shifted upwards without changing the shape of the activation potential, the peak potential, the reversal potential and the curve at a rate of 49.34% ± 9.78% (n = 7, p <0.05) , 40μmol / L of ginsenoside Rb1 decreased the maximum activation peak potential of Itof from 35.342 ± 3.126pA / pF to 26.783 ± 4.153pA / pF with the inhibition rate of 24.21% ± 8.35% (n = 8, p <0.05) , IV curve down. The steady-state activation curves fitted by the Boltemann equation were not significantly affected by the two-channel current before and after administration, but the drug accelerated the steady-state inactivation and slowed the recovery after inactivation (n = 7, p <0.05) Rb1 mainly inhibits itof (peak potential), which is a fast current component of Ito, and has no significant effect on the slow current component Itos (sustain potential). Conclusion Ginsenoside Rb1 has a significant inhibitory effect on the currents of Ica, L and Ito channels, but does not change the channel kinetics of Ica and L channels.
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