KB-R7943对豚鼠心室肌细胞振荡式Na~+/Ca~(2+)交换电流的影响

目的观察Na+/Ca2+交换体阻滞剂KB-R7943(KBR)对豚鼠心室肌细胞振荡式Na+/Ca2+交换电流(INCX)的影响。方法采用全细胞膜片钳技术,利用去极化电压脉冲刺激诱发细胞膜产生振荡式电流,在不同的离子环境下,记录KBR对这一电流的影响。结果该振荡式电流的产生与细胞内钙超载引起的肌质网钙释放有关,它的主要成分是Na+/Ca2+交换电流,与细胞膜的阴离子通道无关。KBR对振荡式INCX的抑制作用具有剂量依赖性,对外向和内向振荡电流的抑制率无差异,两者的半数抑制浓度均约为4μmol/L。结论KBR可抑制振荡式INCX,其抑制作用与实验条件下的离子环境有关,与Na+/Ca2+交换体的运转模式无关。

Effect of KB-R7943 on oscillatory Na~+/Ca~(2+) exchange current in guinea-pig ventricular myocytes

Objective To investigate the effect of KBR on oscillatory I NCX in guinea-pig ventricular myocytes. Methods Whole-cell clamp was performed with the pipette solution containing(mmol/L) 0.1 EDTA,120 Cs + and 20 or 10 Na + and the external solution containing(mmol/L) 1 Ca 2+,140 Na +,0.02 ouabain and 0.01D600.Inward and outward oscillatory I NCX were evoked at-60 mV and +30 mV respectively. Results KBR(1~30μmol/L) inhibited oscillatory I NCX in a concentration-dependent manner with IC50s of about 4μmol/L at-60 mV and +30 mV.KBR at 20~30μmol/L completely inhibited I NCX at each voltage investigated.I NCX was also completely abolished by 5μmol/L ryanodine,but 1 mmol/L DADS (4,4′-dinitrostilbene-2,2′-disulfonic acid) did not affect it. Conclusion The oscillatory current mainly consists of I NCX under the ionic conditions,and KBR inhibits outward and inward oscillatory I NCX with almost equal potency.