毒蕈碱通过大鼠背外侧隔核神经元中的M4受体增加非电压依赖性钾电导。

Muscarine increases a voltage-independent potassium conductance through an M4 receptor in rat dorsolateral septal nucleus neurons.

作者信息

Hasuo H, Akasu T, Gallagher J P

机构信息

Department of Physiology, Kurume University School of Medicine, Japan.

出版信息

Neurosci Lett. 1995 Apr 21;189(3):163-6. doi: 10.1016/0304-3940(95)11483-d.

DOI:10.1016/0304-3940(95)11483-d

PMID:7624035

Abstract

The direct effect of muscarine on neurons of the rat dorsolateral septal nucleus (DLSN) was examined by using conventional microelectrode and voltage-clamp techniques. Muscarine (1-50 microM) caused a hyperpolarization accompanied by an increase of a voltage-independent potassium conductance. Pirenzepine competitively antagonized the muscarine-induced hyperpolarization with an apparent dissociation constant (Kd) value of 54 nM. Furthermore, intracellular loading with GTP gamma S, a non-hydrolyzable GTP analog, blocked irreversibly the muscarine-induced hyperpolarization. In addition, pretreatment of neurons with pertussis toxin (PTX) prevented the hyperpolarization produced by muscarine. These results suggest that muscarine hyperpolarizes DLSN neurons via a voltage-independent potassium conductance by acting at M4 subtype receptors which are coupled to a PTX-sensitive G-protein in DLSN neurons.

摘要

采用传统微电极和电压钳技术研究了毒蕈碱对大鼠背外侧隔核（DLSN）神经元的直接作用。毒蕈碱（1 - 50微摩尔）引起超极化，同时伴有非电压依赖性钾电导增加。哌仑西平竞争性拮抗毒蕈碱诱导的超极化，其表观解离常数（Kd）值为54纳摩尔。此外，用不可水解的GTP类似物GTPγS进行细胞内加载，不可逆地阻断了毒蕈碱诱导的超极化。另外，用百日咳毒素（PTX）预处理神经元可防止毒蕈碱产生的超极化。这些结果表明，毒蕈碱通过作用于DLSN神经元中与PTX敏感G蛋白偶联的M4亚型受体，经非电压依赖性钾电导使DLSN神经元超极化。