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ACh recognition and modulation of the inhibitory nicotinic ACh receptor

抑制性烟碱 ACh 受体的 ACh 识别和调节

基本信息

批准号：
08680723
负责人：
NAGAHAMA Tatsumi
金额：
$ 1.54万
依托单位：
KOBE UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08680723/
关键词：
inhibitory ACh receptor Cl^- channel Lophotoxin Bippinatin nicotinic receptor ACh binding site Aplysia IJP Cl-チャンネルシナプス修飾 Bipinnatin

项目摘要

Firing of Aplysia cholinergic MA neurons produces IPSPs in the jaw-closing (JC) motor neurons and IJPs in the JC muscle fibers. We previously demonstrated that the ACh receptors producing these inhibitory responses may be nicotinic, and the muscle receptors may be associated with Cl^- channel. Lophotoxin and the three analogues (bippinatin-A,B,C)are known to react covalently with Tyr^<190> in the ACh binding site of the receptor and inhibit the function. Bimolecular reaction constants decreased in the order bippinatin-B>A>C for the ACh binding site. In the present study the effects of these analogues on the IJPs or IPSPs were explored and compared with those on the excitatory responses to know the ACh recognition of the inhibitory ACh receptors. Bippinatin-B largely reduced the size of the IJPs, while bippinatin-A and -C increased it. The voltage clamp experiments of the JC neurons showed that the reversal potential of the synaptic current response was shifted toward more positive when the Cl^- was imjected into the JC neurons, suggesting that the ACh receptor in the JC neurons also may be associated with Cl^- channel. Bippinatin-B largely reduced the size of the IPSPs while bippinatin-A initially increased it (ca.25%) and reduced it later. The effect of bippinatin-C was more complex. Initially bippinatin-C largely increased the IPSP size (ca.200%) and then reduced it. After that the MA firing tended to produce the large depolarizing response and finally all responses ceased. These results suggest that the ACh binding site of the inhibitory receptor may be similar to that of the excitatory ACh receptor but the fine molecular structure around the binding site may be different between them.

胆碱能MA神经元的放电在下颌闭合（JC）运动神经元中产生IPSP，并在JC肌纤维中产生IJPs。我们以前证明产生这些抑制反应的ACh受体可能是烟碱型的，肌肉受体可能与Cl^-通道有关。已知Lophotoxin和三种类似物（bippinatin-A、B、C）与<190>受体的ACh结合位点中的Tyr 1共价反应并抑制功能。乙酰胆碱结合位点的双分子反应常数按bippinatin-B>A>C的顺序减小。本研究探讨了这些类似物对IJPs或IPSP的影响，并与兴奋性反应进行了比较，以了解抑制性ACh受体对ACh的识别。JC神经元的电压钳实验表明，当Cl^-注入JC神经元时，JC神经元突触电流反应的反转电位向正方向移动，提示JC神经元上的ACh受体可能与Cl^-通道有关。bippinatin-B在很大程度上减少了IPSPs的大小，而bippinatin-A最初增加了它（约25%），后来又减少了它。bippinatin-C的作用更为复杂。bippinatin-C使IPSP的大小先增大约200%，然后减小，之后MA放电趋向于产生大的去极化反应，最后所有反应停止。这些结果表明，抑制性受体的ACh结合位点可能是类似的兴奋性ACh受体，但结合位点周围的精细分子结构可能是不同的。