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The study of sodium channels involved in pain responses using specific modulators

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Author:: No author available

Journal Title:: ACTA PHYSIOLOGICA SINICA

Issue:: 5

DOI:: No doi available

Key Word:: voltage-gated sodium channel;sodium channel-specific modulator;nociception;anti-nociception

Abstract： 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) axe investigated to be sodium channel-specific modulators. The α-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 β-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. Howevor 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 targetingVGSCs.

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