ISSN 0371-0874, CN 31-1352/Q

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

JI Yong-Hua, LIU Tong

School of Life Sciences, Shanghai University, Shanghai 200444, China; Graduate School of the Chinese Academy of Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

摘要

Voltage-gated sodium channels (VGSCs) are transmembrane proteins responsible for generation and conduction of actionpotentials in excitable cells. Physiological and pharmacological studies have demonstrated that VGSCs play a critical role in chronicpain associated with tissue or nerve injury. Many long-chain peptide toxins (60-76 amino acid residues) purified from the venom ofAsian scorpion Buthus martensii Karsch (BmK) are investigated to be sodium channel-specific modulators. The -like neurotoxins thatcan 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 -like neurotoxins that can bind to receptor site 4 of sodium channels, named as BmK AS, BmK AS-1 and BmK IT2, could producepotent 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 smallDRG neurons. Moreover, BmK ASs could decrease the excitability of small DRG neurons. Thus, the nociception/anti-nociceptioninduced 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 betterunderstanding the roles of VGSCs in pain signal conduction, but also lead molecules in the development of ideal analgesics targetingVGSCs.

关键词: voltage-gated sodium channel; sodium channel-specific modulator; nociception; anti-nociception

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

JI Yong-Hua, LIU Tong

School of Life Sciences, Shanghai University, Shanghai 200444, China; Graduate School of the Chinese Academy of Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

Abstract

Voltage-gated sodium channels (VGSCs) are transmembrane proteins responsible for generation and conduction of actionpotentials in excitable cells. Physiological and pharmacological studies have demonstrated that VGSCs play a critical role in chronicpain associated with tissue or nerve injury. Many long-chain peptide toxins (60-76 amino acid residues) purified from the venom ofAsian scorpion Buthus martensii Karsch (BmK) are investigated to be sodium channel-specific modulators. The -like neurotoxins thatcan 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 -like neurotoxins that can bind to receptor site 4 of sodium channels, named as BmK AS, BmK AS-1 and BmK IT2, could producepotent 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 smallDRG neurons. Moreover, BmK ASs could decrease the excitability of small DRG neurons. Thus, the nociception/anti-nociceptioninduced 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 betterunderstanding the roles of VGSCs in pain signal conduction, but also lead molecules in the development of ideal analgesics targetingVGSCs.

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

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通讯作者:JI Yong-Hua  E-mail: yhji@staff.shu.edu.cn

引用本文:

JI Yong-Hua, LIU Tong. The study of sodium channels involved in pain responses using specific odulators[J]. 生理学报 2008; 60 (5): 628-634.

JI Yong-Hua, LIU Tong. The study of sodium channels involved in pain responses using specific odulators. Acta Physiol Sin 2008; 60 (5): 628-634 (in Chinese with English abstract).