Scorpion toxin BmK I directly activates Nav1.8 in primary sensory neurons to induce neuronal hyperexcitability in rats |
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| Authors: | Pin Ye Yunlu Jiao Zhenwei Li Liming Hua Jin Fu Feng Jiang Tong Liu Yonghua Ji |
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| Affiliation: | 1. Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200436, China2. 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 |
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| 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. |
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| Keywords: | voltage-gated sodium channel Nav1.8 primary sensory neurons BmK I |
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