Voltage-gated sodium channels (VGSCs) are transmembrane
proteins responsible for generation and conduction of action potentials in excitable cells. Physiological and pharmacological studies have demonstrated that VGSCs play a critical role in
chronic pain associated with tissue or nerve injury. Many long-chain
peptide toxins (60-76
amino acid residues) purified from the
venom of Asian scorpion Buthus martensii Karsch (BmK) are investigated to be
sodium channel-specific modulators. The alpha-like
neurotoxins that can bind to receptor site 3 of
sodium channels, named as
BmK I and
BmK abT, could induce nociceptive effects in rats. On the contrast, the beta-like
neurotoxins that can bind to receptor site 4 of
sodium channels, named as
BmK AS,
BmK AS-1 and
BmK IT2, could produce potent anti-nociceptive effects in animal
pain models.
BmK I could strongly prolong the fast inactivation of
tetrodotoxin (TTX)-sensitive Na(+) currents on the rat dorsal root ganglia (DRG) neurons together with the augmentation of peak current amplitude. However,
BmK IT2 and BmK ASs, potently suppressed both the peak TTX-resistant and TTX-sensitive Na(+) currents on rat small DRG neurons. Moreover, BmK ASs could decrease the excitability of small DRG neurons. Thus, the nociception/anti-nociception induced by scorpion
neurotoxins may attribute to their distinct modulation on
sodium channels in primary afferent sensory neurons. Therefore, the
sodium channel-specific modulators from BmK
venom could be used as not only pharmacological tools for better understanding the roles of VGSCs in
pain signal conduction, but also lead molecules in the development of ideal
analgesics targeting VGSCs.