Nicotinic acetylcholine receptors in mouse and rat optic nerves.
Nicotinic acetylcholine receptors in mouse and rat optic nerves.
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小鼠和大鼠视神经中的烟碱乙酰胆碱受体。
DOI：
10.1152/jn.00769.2003
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Chiu,ShingYan
中科院分区：
文献类型：
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作者：
Zhang,Chuan-Li;Verbny,Yakov;Malek,SamehA;Stys,PeterK;Chiu,ShingYan
通过用钙指示剂选择性染色轴突群体来检查小鼠和大鼠视神经轴突中受体介导的钙信号传导。尼古丁（1-50 μM）诱导轴突钙升高，当从浴中除去钙时，该升高被消除，表明尼古丁诱导钙流入轴突。尼古丁反应被d-筒箭毒碱和美加明阻断，但不被α-银环蛇毒素阻断，表明存在钙渗透性非α7烟碱乙酰胆碱受体（nAChR）亚型。引起轴突nAChR钙反应的激动剂效力顺序为金雀花碱>烟碱>乙酰胆碱。尼古丁介导的钙反应在正常髓鞘形成过程中减弱，从P1（有髓鞘）到P30（有髓鞘）减少约10倍。尼古丁还引起新生儿视神经复合动作电位的快速降低，这与非特异性阳离子烟碱通道开放后膜的分流一致。电压门控钙通道在nAChR激活过程中对轴突钙升高的贡献很小。在重复的刺激过程中，新生小鼠视神经的复合动作电位经历了一个逐渐减少的幅度，可以部分地防止d-筒箭毒碱，这表明激活轴突AChRs的活性依赖性释放乙酰胆碱。我们的结论是，哺乳动物视神经轴突表达nAChRs，并建议这些受体在视神经发育过程中以活性依赖的方式激活，以调节轴突的兴奋性和生物学。
Receptor-mediated calcium signaling in axons of mouse and rat optic nerves was examined by selectively staining the axonal population with a calcium indicator. Nicotine (1-50 μM) induced an axonal calcium elevation that was eliminated when calcium was removed from the bath, suggesting that nicotine induces calcium influx into axons. The nicotine response was blocked by d-tubocurarine and mecamylamine but not α-bungarotoxin, indicating the presence of calcium permeable, non-α7 nicotinic acetylcholine receptor (nAChR) subtype. Agonist efficacy order for eliciting the axonal nAChR calcium response was cytisine ∼ nicotine >> acetylcholine. The nicotine-mediated calcium response was attenuated during the process of normal myelination, decreasing by approximately 10-fold from P1 (premyelinated) to P30 (myelinated). Nicotine also caused a rapid reduction in the compound action potential in neonatal optic nerves, consistent with a shunting of the membrane after opening of the nonspecific cationic nicotinic channels. Voltagegated calcium channels contributed little to the axonal calcium elevation during nAChR activation. During repetitive stimulations, the compound action potential in neonatal mouse optic nerves underwent a gradual reduction in amplitude that could be partially prevented by d-tubocurarine, suggesting an activity-dependent release of acetylcholine that activates axonal AChRs. We conclude that mammalian optic nerve axons express nAChRs and suggest that these receptors are activated in an activity-dependent fashion during optic nerve development to modulate axon excitability and biology.