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.
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