White Sean H, Carter Christopher J, Magoski Neil S
Department of Biomedical and Molecular Sciences, Physiology Graduate Program, Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada.
Department of Biomedical and Molecular Sciences, Physiology Graduate Program, Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada
J Neurophysiol. 2014 Jul 15;112(2):446-62. doi: 10.1152/jn.00796.2013. Epub 2014 Apr 16.
Nicotinic receptors form a diverse group of ligand-gated ionotropic receptors with roles in both synaptic transmission and the control of excitability. In the bag cell neurons of Aplysia, acetylcholine activates an ionotropic receptor, which passes inward current to produce a long-lasting afterdischarge and hormone release, leading to reproduction. While testing the agonist profile of the cholinergic response, we observed a second current that appeared to be gated only by nicotine and not acetylcholine. The peak nicotine-evoked current was markedly smaller in magnitude than the acetylcholine-induced current, cooperative (Hill value of 2.7), had an EC50 near 500 μM, readily recovered from desensitization, showed Ca(2+) permeability, and was blocked by mecamylamine, dihydro-β-erythroidine, or strychnine, but not by α-conotoxin ImI, methyllycaconitine, or hexamethonium. Aplysia transcriptome analysis followed by PCR yielded 20 full-length potential nicotinic receptor subunits. Sixteen of these were predicted to be cation selective, and real-time PCR suggested that 15 of the 16 subunits were expressed to varying degrees in the bag cell neurons. The acetylcholine-induced current, but not the nicotine current, was reduced by double-strand RNA treatment targeted to both subunits ApAChR-C and -E. Conversely, the nicotine-evoked current, but not the acetylcholine current, was lessened by targeting both subunits ApAChR-H and -P. To the best of our knowledge, this is the first report suggesting that a nicotinic receptor is not gated by acetylcholine. Separate receptors may serve as a means to differentially trigger plasticity or safeguard propagation by assuring that only acetylcholine, the endogenous agonist, initiates large enough responses to trigger reproduction.
烟碱型受体构成了一组多样的配体门控离子型受体，在突触传递和兴奋性控制中均发挥作用。在海兔的袋状细胞神经元中，乙酰胆碱激活一种离子型受体，该受体通过内向电流产生持久的后放电和激素释放，从而引发生殖行为。在测试胆碱能反应的激动剂谱时，我们观察到第二种电流，它似乎仅由尼古丁而非乙酰胆碱门控。尼古丁诱发的电流峰值在幅度上明显小于乙酰胆碱诱导的电流，具有协同性（希尔系数为2.7），半数有效浓度（EC50）接近500μM，易于从脱敏状态恢复，显示出钙离子通透性，并且被美加明、二氢-β-刺桐碱或士的宁阻断，但不被α-芋螺毒素ImI、甲基lycaconitine或六甲铵阻断。对海兔转录组进行分析，随后通过聚合酶链反应（PCR）得到了20个全长潜在烟碱型受体亚基。其中16个预计为阳离子选择性，实时PCR表明这16个亚基中有15个在袋状细胞神经元中不同程度地表达。靶向亚基ApAChR-C和-E的双链RNA处理可降低乙酰胆碱诱导的电流，但不影响尼古丁电流。相反，靶向亚基ApAChR-H和-P可减少尼古丁诱发的电流，但不影响乙酰胆碱电流。据我们所知，这是首次报道表明烟碱型受体不由乙酰胆碱门控。不同的受体可能作为一种手段，通过确保只有内源性激动剂乙酰胆碱引发足够大的反应来触发生殖行为，从而差异性地触发可塑性或保障信号传播。
