Scorpion toxin BmK I directly activates Nav1.8 in primary sensory neurons to induce neuronal hyperexcitability in rats.
10.1007/s13238-015-0154-4
- Author:
Pin YE
1
;
Yunlu JIAO
;
Zhenwei LI
;
Liming HUA
;
Jin FU
;
Feng JIANG
;
Tong LIU
;
Yonghua JI
Author Information
1. Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai, 200436, China.
- Publication Type:Journal Article
- MeSH:
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
- From:
Protein & Cell
2015;6(6):443-452
- CountryChina
- Language:English
-
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.
