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首页> 外文会议>International Congress on Electrocardiology >DIFFERENTIAL EFFECTS OF MEFENAMIC ACID ON CARDIAC I_(ks) AND THE KCNQ1/KCNE1 CHANNELS
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DIFFERENTIAL EFFECTS OF MEFENAMIC ACID ON CARDIAC I_(ks) AND THE KCNQ1/KCNE1 CHANNELS

机译：Mefenamic acid对心脏I_（ks）和Kcnq1 / Kcne1通道的差异效应

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Mefenamic acid is a nonsteroidal anti-inflammatory agent and affects a variety of ion channels. In the present study, we investigated the effects of mefenamic acid on native I_(ks) channels in guinea-pig atrial cells and heteromeric KCNQl/fCCNEl channels expressed in COS-7 cells, using the whole-cell patch-clamp technique. Both I_(Ks) and KCNQ1/KCNE1 currents were identified as the chroraanol 293B-sensitive current. The KCNQ1/KCNE1 channel exhibited the voltage- and time-dependent activation during depolarizing voltage-clamp steps applied from a holding potential of -80 mV. Bath application of 0.1 mM mefenamic acid markedly increased the amplitude of instantaneous outward current but decreased the time-dependent current of the KCNQ1/KCNE1 channel upon depolarizations. These changes in current properties in the presence of mefenamic acid were facilitated during repetitive depolarizations. Mefenamic acid thus appears to stabilize the KCNQ1/KCNE1 channel in its open state; the channels once activated by depolarization hardly deactivate upon repolarization. In contrast, native I_(Ks) was scarcely affected by mefenamic acid at concentrations up to 1 mM, with the exception that the deactivation kinetics was slightly slowed, which suggests that mefenamic acid does not appreciably affect I_(Ks) in vivo. We conclude that native I_(Ks) and the reconstituted KCNQ1/KCNE1 channels represent a marked differential sensitivity to mefenamic acid.
机译：Mefenamic acid是一种非甾体抗炎剂，并影响各种离子通道。在本研究中，我们使用全细胞贴片钳技术研究了在COS-7细胞中表达的几内亚猪心房细胞和异统KCNQL / FCC罐通道的天然I_（KS）通道对梅青酸的影响。 I_（KS）和KCNQ1 / KCNE1电流被识别为Chroraanol 293B敏感电流。 KCNQ1 / Kcne1通道在从保持电位的去极化电压 - 夹持步骤期间表现出电压和时间依赖性的激活，从而从保持电位为-80mV。浴施施加0.1mM梅芬酸明显增加瞬时外流的幅度，但在去极化时降低了KCNQ1 / Kcne1通道的时间依赖性电流。在重复的去偏振期间促进了在存在梅芬酸存在下的目前性质的变化。因此，Mefenamic acid似乎在其开放状态下稳定KCNQ1 / Kcne1通道;通过去极化激活的通道几乎在复极性时难以停用。相反，天然I_（KS）几乎没有受到1mm的浓度的浓度影响，除了停用动力学略微放缓，这表明梅芬酸不会显着影响体内I_（KS）。我们得出结论，天然I_（KS）和重构的KCNQ1 / KCNE1通道代表了对梅青酸的明显差异敏感性。

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