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Scorpion toxin BmKI directly activates Nav1.8 in primary sensory neurons to induce neuronal hyperexcitability in rats
  • 时间:0
  • 分类:Q954.671[生物学—动物学] Q959.226.4[生物学—动物学]
  • 作者机构:[1]Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200436, China, [2]Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and the Second Affiliated Hospital of Soochow University, Institute of Neuroscience, Soochow University, Suzhou 215021, China
  • 相关基金:J.Y.H was supported by the National Basic Research Program (973 Program) (No. 2010CB529806), partially by grants from National Nat- ural Science Foundation of China (Grant Nos. 31171064 and 81402903) and Key Research Program of Science and Technology Commissions of Shanghai Municipality (11JC1404300, 13DJ 1400300). L.T. was supported by grants from National Natural Science Foundation of China (Grant Nos. 31371179 and 81300968) and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
中文摘要:

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。

英文摘要:

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.

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