The effects of sevoflurane and propofol on QT interval and heterologously expressed human ether-a-go-go related gene currents in xenopus oocytes
The effects of sevoflurane and propofol on QT interval and heterologously expressed human ether-a-go-go related gene currents in xenopus oocytes
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DOI：
10.1213/01.ane.0000184257.54917.99
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发表时间：
2006-01-01
影响因子：
5.7
通讯作者：
Akbarali, HI
中科院分区：
文献类型：
--
作者：
Yamada, M;Hatakeyama, N;Akbarali, HI
七氟醚可通过抑制动作电位复极化相而延长心脏QT间期。这可能是人类以太-a-go-go相关基因（HERG）通道受到抑制的结果。为了阐明麻醉药对HERG通道的作用机制，我们监测了豚鼠在七氟醚和异丙酚存在下的心电图并测量了QT间期。七氟醚（1% ~ 4%）延长QTc呈剂量依赖性（7.5% ~ 21.2%），异丙酚对QTc无影响。此外，HERG通道在爪蟾卵母细胞中得到表达，并在- 70 mV的保持电位下获得向外的HERG电流。从正的测试电位再极化到- 70 mV，导致大的向外尾电流。七氟醚（1%-4%）以紧密依赖的方式抑制HERG向外尾部电流（9.7%-26.6%），而稳态电流仅在大浓度下被抑制。七氟醚的存在降低了聚合电流的时间常数，但失活和活化曲线没有发生移位。异丙酚在临床相关浓度范围内不影响这些电流。综上所述，与稳态电流相比，七氟醚对向外尾部电流的抑制作用更强，表明七氟醚可能在失活状态下调节HERG通道动力学。
Sevoflurane can induce prolongation of the cardiac QT interval by inhibiting the repolarization phase of the action potential. This may occur as a result of inhibition of the human ether-a-go-go related gene (HERG) channel. To clarify the mechanisms of anesthetics on HERG channels, we monitored the electrocardiogram and measured QT intervals in the guinea pig in the presence of sevoflurane and propofol. Sevoflurane (1%-4%) prolonged QTc dose-dependently (7.5%-21.2%), but propofol did not affect it. Furthermore, HERG channels were expressed in Xenopus oocytes and outward HERG currents were obtained on step depolarization from a holding potential of - 70 mV. Repolarization to - 70 mV from positive test potentials resulted in large outward tail currents. Sevoflurane (1%-4%), in a close-dependent manner, inhibited the HERG outward tail currents (9.7%-26.6%), whereas steady-state currents were inhibited only at large concentrations. The time constant of the converging current was decreased in the presence of sevoflurane, but the inactivation and activation curves were not shifted. Propofol did not affect these currents within the clinically relevant concentration. In conclusion, compared with steady-state currents, sevoflurane was more potent in inhibiting the outward tail currents, suggesting that sevoflurane may modulate the HERG channel kinetics in its inactivated state.