title: 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.affiliation: Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai, 200436, China.
authors.forename: Pin
authors.initials: P
authors.lastname: Ye
authors.forename: Yunlu
authors.initials: Y
authors.lastname: Jiao
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Li
authors.forename: Liming
authors.initials: L
authors.lastname: Hua
authors.forename: Jin
authors.initials: J
authors.lastname: Fu
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Ji
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D048429:Cell Size; D002478:Cells, Cultured; D055724:Electrophysiological Phenomena / Q000187:drug effects; D005663:Furans / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D007700:Kinetics; D008297:Male; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012605:Scorpions; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D061585:Voltage-Gated Sodium Channel Agonists / Q000494:pharmacology*
chemical_list: C520740:A 803467; D000814:Aniline Compounds; D005663:Furans; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568319:Scn10a protein, rat; D012604:Scorpion Venoms; D026941:Sodium Channel Blockers; D061585:Voltage-Gated Sodium Channel Agonists; C105338:makatoxin I