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

Protein Cell. 2015 Jun;6(6):443-52. doi: 10.1007/s13238-015-0154-4. Epub 2015 Apr 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Scorpion Venoms / pharmacology*
  • Scorpions*
  • Sensory Receptor Cells / drug effects*
  • Sensory Receptor Cells / metabolism
  • Sensory Receptor Cells / physiology*
  • Sodium Channel Blockers / pharmacology
  • Voltage-Gated Sodium Channel Agonists / pharmacology*

Substances

  • 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