【摘 要】
：
Cobrotoxin (CbT), a short-chain postsynaptic α-neurotoxin, has been reported to play a role in analgesia.However, to date, the detailed mechanisms still remain unknown.In the present study, we identif
【机 构】
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Key Laboratory of Pain Research & Therapy, Department of Neurobiology and Medical Psychology, Medica
【出 处】
：
中国神经科学学会第九届全国学术会议暨第五届会员代表大会
论文部分内容阅读
Cobrotoxin (CbT), a short-chain postsynaptic α-neurotoxin, has been reported to play a role in analgesia.However, to date, the detailed mechanisms still remain unknown.In the present study, we identify a novel functional role of CbT in modulating T-type Ca2+ channel currents (T-currents) in small dorsal root ganglia (DRG) neurons as well as pain behaviors in mice.We found that CbT inhibited T-currents in a dose-dependent manner.CbT at 1 μM reversibly inhibited T-currents by ~26.3%.This inhibitory effect was abolished by the non-selective muscarinic acetylcholine receptor (mAChR) antagonist atropine, or the selective M3 mAChR antagonist 4-DAMP, while naloxone, an opioid receptor antagonist had no effect.Intracellular infusion of GDP-β-S or pretreatment of the ceils with pertussis toxin (PTX) completely blocked the inhibitory effects of CbT Using depolarizing prepulse, we found the absence of direct binding between G-protein βγsubunits and T-type Ca2+ channels in CbT-induced T-current inhibition.CbT responses were abolished by the phospholipase C inhibitor U73122 (but not the inactive analog U73343).The classical and novel protein kinase C (nPKC) antagonist chelerythrine chlorid or GFl09203X abolished CbT responses, whereas the classical PKC antagonist Ro31-8820 or inhibition of PKA elicited no such effects.Intrathecal administration of CbT (5 μg/kg) produced antinociceptive effects in mechanical, thermal, and inflammatory pain models.Moreover, CbT-induced antinociception could be abrogated by 4-DAMP.Taken together, these results suggest that CbT acting through M3 mAChR inhibits T-currents via a PTX-sensitive nPKC pathway in small DRG neurons, which could contribute to its analgesic effects in mice.
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