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

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 small-sized (<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.
Authors	Pin Ye, Yunlu Jiao, Zhenwei Li, Liming Hua, Jin Fu, Feng Jiang, Tong Liu, Yonghua Ji
Journal	Protein & cell (Protein Cell) Vol. 6 Issue 6 Pg. 443-52 (Jun 2015) ISSN: 1674-8018 [Electronic] Germany
PMID	25903152 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	A 803467 Aniline Compounds Furans NAV1.8 Voltage-Gated Sodium Channel Scn10a protein, rat Scorpion Venoms Sodium Channel Blockers Voltage-Gated Sodium Channel Agonists makatoxin I
Topics	Aniline Compounds (pharmacology) Animals Cell Size Cells, Cultured Electrophysiological Phenomena (drug effects) Furans (pharmacology) Ganglia, Spinal (cytology) Kinetics Male NAV1.8 Voltage-Gated Sodium Channel (metabolism) Rats Rats, Sprague-Dawley Scorpion Venoms (antagonists & inhibitors, pharmacology) Scorpions Sensory Receptor Cells (drug effects, metabolism, physiology) Sodium Channel Blockers (pharmacology) Voltage-Gated Sodium Channel Agonists (pharmacology)

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