牛磺酸镁对缺氧/复氧致大鼠心肌细胞内向整流钾通道异常的影响

目的观察牛磺酸镁配合物(taurine magnesium coordi-nation compound,TMCC)对缺氧/复氧损伤所致大鼠心肌细胞异常内向整流钾通道电流(Ik1)的影响。方法采用Lan-gendorff逆行主动脉灌流酶溶液消化法急性分离大鼠单个心肌细胞,在电压钳模式下,应用全细胞膜片钳技术记录不同浓度TMCC对正常细胞和不同浓度TMCC及胺碘酮对缺氧/复氧模型细胞内向整流钾通道电流Ik1的变化。结果不同浓度TMCC对正常大鼠心肌细胞的Ik1无明显性影响。缺氧/复氧能使Ik1内向电流峰值从(-13.05±1.43)pA.pF-1降至(-6.94±0.59)pA.pF-1(n=6,P<0.01),内向电流曲线上移。与缺氧/复氧组相比,TMCC(100、200、400μmol.L-1)可使减小的内向电流峰值分别恢复为(-7.21±0.79)pA.pF-1、(-7.28±0.22)pA.pF-1、(-10.96±0.78)pA.pF-1(n=6,P<0.01),24.24μmol.L-1胺碘酮使其恢复为(-8.80±0.97)pA.pF-1。TMCC(100、200、400μmol.L-1)和胺碘酮均可使上移的内向电流曲线下移。缺氧/复氧使大鼠心肌细胞Ik1外向电流峰值从(2.43±0.32)pA.pF-1降至(1.31±0.28)pA.pF-1,I-V曲线下移。与缺氧/复氧组相比,TMCC(100、200、400μmol.L-1)可使减小的外向电流分别恢复为(0.90±0.14)pA.pF-1、(1.84±0.46)pA.pF-1、(2.36±0.40)pA.pF-1、24.24μmol.L-1胺碘酮使其恢复为(2.16±0.69)pA.pF-1。TMCC(100、200、400μmol.L-1)和胺碘酮均可使下移的外向电流曲线上移。结论 TMCC对正常心肌细胞Ik1无影响,但能恢复缺氧/复氧减小的Ik1内向电流和外向电流峰值。提示TMCC对Ik1的作用可能是其发挥抗心律失常的机制之一。

Effects of taurine-magnesium coordination compound on abnormal inward rectifier potassium channel current induced by hypoxia-reoxygenation in cardiomyocytes of rats

Aim To investigate the antiarrhythmic mechanism of taurine magnesium coordination compound on abnormal inward rectifier potassium current(Ik1) induced by hypoxia-reoxygenation in cardiomyocytes of rats.Methods Enzymatic dissociation through Langendorff retrograde aortic perfusion was used to get single rat ventricular myocytes.In voltage clamp mode,whole-cell patch clamp was used to record Ik1 in normal cardiomyocytes and single rat ventricular cardiomyocytes of arrhythmia induced by hypoxia-reoxygenation.Results TMCC had no effect on Ik1 from normal cardiomyocytes.Compared to the control group,the inward current peak of Ik1 in the hypoxia-reoxygenation model was reduced significantly(-13.05±1.431 pA·pF-1 vs-6.94±0.59 pA·pF-1,n=6 P<0.01),and the inward current I-U curve of Ik1 shifted upward.Compared with hypoxia / reoxygenation group,TMCC(100,200,400 μmol·L-1)restored the inward current peak of Ik1 to(-7.21 ± 0.79) pA·pF-1,(-7.28±0.22) pA·pF-1,(-10.96 ± 0.78) pA·pF-1(n=6,P<0.01),24.24 μmol·L-1 amiodarone restored it to(-8.80 ± 0.97) pA.pF-1,and shifted the I-V curve downward.Besides,compared to the control group,the outward current peak of I k1 in the hypoxia-reoxygenation model was reduced significantly(2.43 ± 0.32 pA.pF-1 vs 1.31 ± 0.28 pA.pF-1,P < 0.01),and the outward current I-V curve of I k1 shifted downward.Compared with hypoxia / reoxygenation group,TMCC(100,200,400 μmol.L-1) restored the outward current peak to(0.90 ± 0.14) pA.pF-1,(1.84 ± 0.46) pA.pF-1,(2.36 ± 0.40) pA.pF-1,24.24 μmol.L-1 amiodarone restored it to(2.16 ± 0.69)pA.pF-1,and shifted the I-V curve upward.Conclusions TMCC has no effect on I k1 in normal cardiomyocytes.However,TMCC can restore the inward current and the outward current of I k1,which is reduced by hypoxia-reoxygenation,which suggests that the effect may be one of the mechanisms of anti-hypoxia-reoxygenation-induced arrhythmias of TMCC.