RESEARCH ARTICLE

Scorpion toxin BmK I directly activates Nav1.8 in primary sensory neurons to induce neuronal hyperexcitability in rats

  • Pin Ye 1 ,
  • Yunlu Jiao 1 ,
  • Zhenwei Li 1 ,
  • Liming Hua 1 ,
  • Jin Fu 1 ,
  • Feng Jiang 1 ,
  • Tong Liu , 2 ,
  • Yonghua Ji , 1
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  • 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

Received date: 09 Feb 2015

Accepted date: 05 Mar 2015

Published date: 11 Jun 2015

Copyright

2014 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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. However, 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 smallsized (<25 μm) acutely dissociated DRG neurons, which correlated with its inhibition on both fast and slow inactivation. Moreover, voltage-dependent activation and steady-state inactivation curves of Nav1.8 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 remarkably, suggesting BmK I as a valuable probe for studying Nav1.8. And Nav1.8 is an important target related to BmK I-evoked pain.

Cite this article

Pin Ye , Yunlu Jiao , Zhenwei Li , Liming Hua , Jin Fu , Feng Jiang , Tong Liu , Yonghua Ji . Scorpion toxin BmK I directly activates Nav1.8 in primary sensory neurons to induce neuronal hyperexcitability in rats[J]. Protein & Cell, 2015 , 6(6) : 443 -452 . DOI: 10.1007/s13238-015-0154-4

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