Effects of sevoflurane on voltage-gated sodium channel Nav1.8, Nav1.7, and Nav1.4 expressed in Xenopus oocytes

Effects of sevoflurane on voltage-gated sodium channel Nav1.8, Nav1.7, and Nav1.4 expressed in Xenopus oocytes
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DOI:
10.1007/s00540-011-1167-7
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发表时间:
2011-08-01
影响因子:
2.8
通讯作者:
Uezono, Yasuhito
Uezono, Yasuhito
中科院分区:
医学4区
文献类型:
--
作者:
Yokoyama, Toru;Minami, Kouichiro;Uezono, Yasuhito

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七氟醚是临床上广泛使用的一种挥发性麻醉剂。然而,其机制仍不清楚。最近有报道称,电压门控性钠通道在麻醉机制中具有重要作用。七氟醚对电压依赖性钠通道的影响已经引起了人们的广泛关注。为了阐明这一点,我们研究了七氟醚对非洲爪哇卵母细胞Na-v1.8、Na-v1.4和Na-v1.7表达的影响。采用全细胞双电极电压钳技术,用电生理学方法研究了七氟醚对非洲爪哇卵母细胞Na-v1.8、Na-v1.4和Na-v1.7钠通道的影响。1.0 mM的七氟醚抑制电压门控性钠通道Na(V)1.8、Na(V)1.4和Na(V)1.7,而0.5 mM的七氟醚对钠通道无明显影响。7 mM七氟烷对Na(V)1.8、Na(V)1.4和Na-v 1.7的抑制作用可被蛋白激酶C(PKC)抑制剂双吲哚马来酰亚胺I所完全消除。然而,这些钠通道可能与七氟醚的临床麻醉效果无关。
Sevoflurane is widely used as a volatile anesthetic in clinical practice. However, its mechanism is still unclear. Recently, it has been reported that voltage-gated sodium channels have important roles in anesthetic mechanisms. Much attention has been paid to the effects of sevoflurane on voltage-dependent sodium channels. To elucidate this, we examined the effects of sevoflurane on Na-v 1.8, Na-v 1.4, and Na-v 1.7 expressed in Xenopus oocytes. The effects of sevoflurane on Na-v 1.8, Na-v 1.4, and Na-v 1.7 sodium channels were studied by an electrophysiology method using whole-cell, two-electrode voltage-clamp techniques in Xenopus oocytes. Sevoflurane at 1.0 mM inhibited the voltage-gated sodium channels Na(v)1.8, Na(v)1.4, and Na(v)1.7, but sevoflurane (0.5 mM) had little effect. This inhibitory effect of 1 mM sevoflurane was completely abolished by pretreatment with protein kinase C (PKC) inhibitor, bisindolylmaleimide I. Sevoflurane appears to have inhibitory effects on Na(v)1.8, Na(v)1.4, and Na-v 1.7 by PKC pathways. However, these sodium channels might not be related to the clinical anesthetic effects of sevoflurane.