钌红作为豚鼠离体心室肌细胞钙电流和钠电流的有效阻滞剂。

Ruthenium red as an effective blocker of calcium and sodium currents in guinea-pig isolated ventricular heart cells.

Malécot C O, Bito V, Argibay J A

Physiologie des Cellules Cardiaques et Vasculaires, CNRS UMR 6542, Faculté des Sciences, Tours, France.

Br J Pharmacol. 1998 Jun;124(3):465-72. doi: 10.1038/sj.bjp.0701854.

Abstract

The effect of ruthenium red on calcium and sodium currents was studied in guinea-pig isolated ventricular heart cells with the whole cell patch-clamp technique. 2. Ruthenium red very efficiently blocked the L-type calcium current in a dose-dependent manner. A significant block was observed for concentrations as low as 0.3 microM. Analysis of the dose-response curve with the logistic equation indicated an EC50 of 0.8 microM, a maximum inhibition of 85% reached at 5 microM, and a coefficient of 2.37. 3. There was no shift in the voltage-dependence of the Ca current activation, nor in that of its steady-state inactivation determined with a 1 s prepulse. However, removal of Ca current inactivation at positive voltage was considerably reduced in the presence of concentrations of ruthenium red above 1 microM. A slowing of the time-course of inactivation of the Ca current was also observed. 4. At 10 microM, a concentration generally used to block the sarcoplasmic Ca release channels or the mitochondrial Ca uptake, ruthenium red blocked 26.7+/-4.3% (n=8) of the sodium current, and slowed its inactivation time-course. No effect was observed on the voltage-dependence of the current activation or inactivation. The peak sodium current was also decreased at a 10 times lower concentration by 7.6+/-2.7% (n=3). 5. Thus, at concentrations used to assess intracellular Ca movements, ruthenium red induced in heart cells a significant block of both Ca and Na channels.

摘要

采用全细胞膜片钳技术，研究了钌红对豚鼠离体心室肌细胞钙电流和钠电流的影响。2. 钌红能非常有效地以剂量依赖方式阻断L型钙电流。在低至0.3微摩尔浓度时即可观察到显著阻断作用。用逻辑方程分析剂量-反应曲线表明，半数有效浓度（EC50）为0.8微摩尔，在5微摩尔时最大抑制率达85%，系数为2.37。3. 钙电流激活的电压依赖性以及用1秒预脉冲测定的稳态失活的电压依赖性均未发生改变。然而，在钌红浓度高于1微摩尔时，正电压下钙电流失活的消除明显减少。还观察到钙电流失活时间进程减慢。4. 在通常用于阻断肌浆网钙释放通道或线粒体钙摄取的10微摩尔浓度下，钌红阻断了26.7±4.3%（n = 8）的钠电流，并减慢了其失活时间进程。对电流激活或失活的电压依赖性未观察到影响。在低10倍的浓度下，钠电流峰值也降低了7.6±2.7%（n = 3）。5. 因此，在用于评估细胞内钙转运的浓度下，钌红在心脏细胞中诱导了对钙通道和钠通道的显著阻断。