药物相关性尖端扭转型室性心动过速性别差异的离子通道研究

目的　探讨药物相关性尖端扭转型室性心动过速 (TdP)发生率性别差异的离子流基础。方法　♀、♂兔各 2 0只 ,酶解法分得左室心尖部单个细胞 ,应用全细胞膜片钳技术记录APD、Ito、IK、IK1和ICa ,L。结果　♀、♂兔心肌细胞膜电容差异无显著性 (P >0 0 5 )。♀兔APD90 (5 6 0 4± 2 6 5ms,n =15 )比♂兔APD90 (489 0± 2 0 7)ms ,n =14长 (P <0 0 5 )。IK ,tail、Ito、IK1和ICa,L在♀兔分别为 (0 71± 0 0 5 )pA/ pF、n =17,(8 2 8± 1 0 3) pA/pF、n =18,(2 4 5± 3 6 ) pA/ pF、n =12 ,(9 0± 2 3)pA/ pF、n =15 ,在♂兔分别为 (0 84± 0 0 7) pA/pF、n =18,(8 6 0± 1 2 0 ) pA/pF、n =18,(2 5 9± 4 5 ) pA/pF、n =14 ,(9 3± 2 6 )pA/ pF、n =16。♀兔IK ,tail明显低于♂兔 (P <0 0 5 ) ,而Ito、IK1和ICa,L在♀、♂兔差异无显著性 (P >0 0 5 )。结论　♀兔IK ,tail较低可能是♀兔APD90 较♂兔长及更易发生药物相关性TdP的原因。

Ionic channel research of sex difference in drug-associated torsade de pointes

Aim To investigate the current difference between male and female for elucidating the longer QT interval and higher incidence of drug-associated torsade de pointes in female than in male. Methods Whole cell patch clamp technique was used to record APD, I to, I K,tail, I K1 and I Ca,L of myocytes from left ventricular apex.Results There was no difference in the membrane capacitance between male and female rabbit myocytes. APD 90 was longer in female(560.4±26.5 ms,n=15) than in male(489.0±20.7 ms,n=14), P<0.05. In female rabbit myocytes, I K,tail,I to, I K1 and I Ca,L were (0.71±0.05) pA/pF,n=17,(8.28±1.03) pA/pF, n=18,(24.5±3.6) pA/pF, n=12 and (9.0±2.3) pA/pF, n=15 respectively. In male rabbit myocytes, they were (0.84±0.07) pA/pF,n=18,(8.60 ± 1.20) pA/pF,n=18,(25.9±4.5) pA/pF, n=14 and (9.3±2.6) pA/pF, n=16. I K,tail of female was significantly lower than that of male(P<0.05) and no difference was found in I to, I K1 and I Ca,L between male and female(P>0.05). Conclusions The lower I K,tail of female may play an important role in the longer repolarization, which is responsible for the higher incidence of drug-associated torsade de pointes in female.