The anti-nociceptive effect of BmK AS, a scorpion active polypeptide, and the possible mechanism on specifically modulating voltage-gated Na+ currents in primary afferent neurons.
In the present study, we investigated the anti-nociceptive effect and the underlying mechanism of BmK AS, an active peptide purified from scorpion Buthus martensi Karsch. The results showed that BmK AS can significantly relieve formalin-induced two-phase spontaneous flinching response and carrageenan-induced mechanical hyperalgesia. Using the whole-cell patch-clamp recording, exposure of acutely isolated sensory neurons to 500 nM BmK AS produced a one-fold decrease in the number of action potentials (APs) evoked by a ramp of depolarizing current. To investigate the mechanism of action of BmK AS, isolated membrane current and Ca2+ influx on rat primary sensory neurons were examined. BmK AS produced insignificant effect on voltage-dependent I(K) and KCl or caffeine-induced Ca2+ influx, but caused remarkable suppressive effect on tetrodotoxin-resistant (TTX-R) and tetrodotoxin-sensitive (TTX-S) I(Na). Further experiments showed that BmK AS reduced the peak TTX-R and TTX-S Na+ conductance in a dose-dependent manner, prompted the voltage-dependent activation, and caused a negative shift of the steady-state inactivation of TTX-R and TTX-S I(Na). Thus, the present results indicate the anti-nociceptive response of BmK AS may be ascribed to its specific modulation of voltage-gated Na+ channels of sensory neurons.
Chen
Jin
J
Graduate School of the Chinese Academy of Sciences, Institute of Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, PR China.
Feng
Xing-Hua
XH
Shi
Jian
J
Tan
Zhi-Yong
ZY
Bai
Zhan-Tao
ZT
Liu
Tong
T
Ji
Yong-Hua
YH
D000200:Action Potentials / Q000187:drug effects; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D005557:Formaldehyde / Q000378:metabolism / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D008297:Male; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010147:Pain Measurement; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism; D012604:Scorpion Venoms / Q000494:pharmacology*; D012605:Scorpions; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000378:metabolism; D013779:Tetrodotoxin / Q000378:metabolism; D013997:Time Factors
D000700:Analgesics; C119407:BmK AS polypeptide; D010455:Peptides; D019837:Ryanodine Receptor Calcium Release Channel; D012604:Scorpion Venoms; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D005557:Formaldehyde; D013779:Tetrodotoxin