Motin Leonid, Adams David J
Queensland Brain Institute, University of Queensland, Brisbane, Queensland 4072, Australia.
Neuropharmacology. 2008 Oct;55(5):860-4. doi: 10.1016/j.neuropharm.2008.06.049. Epub 2008 Jul 3.
A number of omega-conotoxins are potent and selective antagonists of N-type voltage-gated calcium channels (VGCCs) and are potentially effective as analgesic agents. omega-Conotoxins CVID and CVIB, venom peptides from Conus catus, inhibit N-type and N/P/Q-type VGCCs, respectively, in rat dorsal root ganglion sensory neurons. In the present study, we tested the effects of five different omega-conotoxins, CVID, CVIB, MVIIA, MVIIC and GVIA, on excitatory synaptic transmission between primary afferents and dorsal horn superficial lamina neurons of rat spinal cord. The N-type VGCC antagonists CVID (200nM) and MVIIA (500nM) completely and irreversibly inhibited excitatory postsynaptic currents (EPSCs) in the dorsal horn superficial lamina. The N- and P/Q-type VGCC antagonist CVIB (200nM) reversibly reduced evoked EPSC amplitude an average of 34+/-8%, whereas MVIIC (200nM) had no effect on excitatory synaptic transmission. In neurons receiving polysynaptic input, CVIB reduced both the EPSC amplitude and the "success rate" calculated as the relative number of primary afferent stimulations that resulted in postsynaptic responses. These results indicate that (i) the analgesic action of omega-conotoxins that antagonise N-type VGCCs may be attributed to inhibition of neurotransmission between primary afferents and superficial dorsal horn neurons, (ii) nociceptive synaptic transmission between primary afferents and superficial lamina neurons is mediated predominantly by N-type VGCCs, and (iii) in contrast to the irreversible inhibition by CVID, MVIIA and GVIA, the inhibition of excitatory monosynaptic transmission by CVIB is reversible.
多种ω-芋螺毒素是N型电压门控钙通道（VGCCs）的强效选择性拮抗剂，具有作为镇痛药的潜在效力。来自芋螺的毒液肽ω-芋螺毒素CVID和CVIB，分别抑制大鼠背根神经节感觉神经元中的N型和N/P/Q型VGCCs。在本研究中，我们测试了五种不同的ω-芋螺毒素，即CVID、CVIB、MVIIA、MVIIC和GVIA，对大鼠脊髓初级传入神经和背角浅层神经元之间兴奋性突触传递的影响。N型VGCC拮抗剂CVID（200nM）和MVIIA（500nM）完全且不可逆地抑制了背角浅层的兴奋性突触后电流（EPSCs）。N型和P/Q型VGCC拮抗剂CVIB（200nM）可使诱发的EPSC幅度平均可逆性降低34±8%，而MVIIC（200nM）对兴奋性突触传递无影响。在接受多突触输入的神经元中，CVIB降低了EPSC幅度以及以引发突触后反应的初级传入刺激的相对数量计算的“成功率”。这些结果表明：（i）拮抗N型VGCCs的ω-芋螺毒素的镇痛作用可能归因于对初级传入神经和背角浅层神经元之间神经传递的抑制；（ii）初级传入神经和浅层神经元之间的伤害性突触传递主要由N型VGCCs介导；（iii）与CVID、MVIIA和GVIA的不可逆抑制作用相反，CVIB对兴奋性单突触传递的抑制是可逆的。
