在主要感觉神经原的电压门钠隧道(VGSC ) 在把疼痛信号传给中央神经系统起一个关键作用。BmK 我, site-3 钠从蝎子 Buthus martensi Karsch 的隧道特定的毒素,在老鼠导致疼痛行为。然而,我不是的 BmK 指向的 VGSC 的子类型完全变清。我们因此调查了 BmK 的效果我在当前的振幅, gating 和 Na 在 DRG 神经原与 neuronal hyperexcitability 被联系的 v 1.8, 。它被发现我 dose-dependently 增加了的那 BmK Na v 1.8 电流在小型(< 25 ? m ) 尖锐地分裂的 DRG 神经原,它在快、慢的 inactivation 上与它的抑制相关。而且,电压依赖者激活和不变的 inactivation Na v 1.8 在一个 hyperpolarized 方向被转移。因此, BmK 我减少了 neuronal 易兴奋性的阀值并且增加了在 DRG 神经原开火的行动潜力。在结论,我们的数据清楚地表明了我调制了的那 BmK Na v 1.8 显著地,建议我为学习 Na v 1.8。并且 Nav1.8 是与 BmK 我唤起疼痛有关的一个重要目标。
Voltage-gated sodium channels (VGSCs) in primary sensory neurons play a key role in transmitting pain signals to the central nervous system. BmK I, a site-3 sodium channel-specific toxin from scorpion Buthus martensi Karsch, induces pain behaviors in rats. How- ever, the subtypes of VGSCs targeted by BmK I were not entirely clear. We therefore investigated the effects of BmK I on the current amplitude, gating and kinetic properties of Nav1.8, which is associated with neuronal hyperexcitability in DRG neurons. It was found that BmK I dose-dependently increased Nav1.8 current in small- sized (〈25 μm) acutely dissociated DRG neurons, which correlated with its inhibition on both fast and slow in- activation. Moreover, voltage-dependent activation and steady-state inactivation curves of Nay1.8 were shifted in a hyperpolarized direction. Thus, BmK I reduced the threshold of neuronal excitability and increased action potential firing in DRG neurons. In conclusion, our data clearly demonstrated that BmK I modulated Nav1.8 re- markably, suggesting BmK I as a valuable probe for studying Nay1.8. And Navl.8 is an important target re- lated to BmK I-evoked pain.