雌激素对小鼠心室肌细胞ATP敏感性钾离子通道活性的影响

目的从离子通道水平,观察雌激素(17α-ethynylestradiol and 17β-estradiol)对小鼠心室肌细胞ATP敏感性钾离子通道的影响。方法利用急性酶解法分离小鼠心室肌细胞,采用膜片钳制技术细胞膜内向外及细胞吸附记录模式。结果在钳制电压-60 mV细胞膜内向外记录模式下,向浴液中加入0.1μmol/L、1μmol/L及10μmol/L三种不同浓度雌激素,观察到两种雌激素(17α-ethynylestradiol、17β-estradiol)均对KATP通道有抑制作用,而且呈浓度依赖性,其半数有效浓度分别为0.3μmol/L及0.1 nmol/L。在钳制电压-60mV细胞吸附记录模式下,向浴液中加入pinacidil或2,4-dinitrophenol(DNP)活化KATP通道后,观察3 min,通道活性未见明显影响。在钳制电压-60mV细胞膜内向外记录模式下,向浴液中加入phorbol 12,13-dibutyrate(PDBu)0.001 nmol与处理后,观察到雌激素(10-8、10-3和1μmol/L)对于KATP离子通道活性抑制作用减弱。结论雌激素可通过影响心肌细胞KATP通道活性防止心律失常的产生,从而发挥心肌保护作用。

Effect of estrogenic agents on ATP-sensitive potassium channel activity in isolated mouse ventricular cardiomyocytes

Objective To study the effects of estrogens（17α-ethynylestradiol and 17β-estradiol） on the ATPsensitive potassium channel（KATP） activities in the enzymatically（collagenase and protease） isolated ICR mouse ventricular cardiomyocytes using inside-out and cell-attached patch clamp techniques. Methods In the inside-out patch configurations,the two estrogens reduced the KATPchannel activities in a dose-dependent manner at- 60 mV holding potential（HP）. Results The half-maximal inhibitory concentration（IC50） of the 17α-esthynylestradiol and the 17β-estradiol were 0. 3 μmol /L and 0. 1 nmol /L,respectively. However,these agents had no effects on the pinacidil-and DNPinduced KATPchannel activities in the cell-attached patch configuration. However,the inhibitory effect of KATPchannelactivities by the 17-estrogens or the anti-estrogens in the excised inside-out patch configuration were abolished by 1 pmol /L PDBu. Conclusions The results of this study demonstrate that some estrogens decrease the KATPchannel activity acting on the inside of the isolated cardiomyocytes,and play a protective role to cardiomyocytes.