Wong L A, Gallagher J P
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
Nature. 1989 Oct 5;341(6241):439-42. doi: 10.1038/341439a0.
Acetylcholine activates both nicotinic and muscarinic receptors in the central nervous system. Although the action of acetylcholine at muscarinic receptor has been well characterized, relatively little is known at the cellular level concerning nicotinic receptor stimulation in brain. Central nicotinic receptors have been implicated in Alzheimer's disease, seizure activity, the generation of slow-wave theta rhythm in the hippocampus and the potential abuse liability of nicotine. At the neuronal level, nicotinic agonists have been most often associated with postsynaptically mediated excitation and membrane depolarization at various sites, including Renshaw spinal motoneurons, locus coeruleus and the medial habenular nucleus. Nicotine acting presynaptically can produce either excitation or inhibition indirectly through the release of endogeneous transmitters or modulators. Whereas a direct inhibitory effect of nicotine has been suggested by one in vivo extracellular recording study in rat cerebellar Purkinje neurons, the mechanism(s) underlying this action is not yet known. We now report our findings obtained using in vitro intracellular methods in a submerged brain slice preparation in which application of nicotinic agonists to rat dorsolateral septal neurons reveal a direct membrane hyperpolarization mediated by an increase in potassium conductance.
乙酰胆碱可激活中枢神经系统中的烟碱型和毒蕈碱型受体。尽管乙酰胆碱对毒蕈碱型受体的作用已得到充分表征，但在细胞水平上，关于脑内烟碱型受体刺激的了解相对较少。中枢烟碱型受体与阿尔茨海默病、癫痫活动、海马体中慢波θ节律的产生以及尼古丁的潜在成瘾性有关。在神经元水平上，烟碱型激动剂最常与包括脊髓闰绍运动神经元、蓝斑和内侧缰核在内的不同部位的突触后介导的兴奋和膜去极化相关。烟碱在突触前起作用时，可通过内源性递质或调节剂的释放间接产生兴奋或抑制作用。虽然一项在大鼠小脑浦肯野神经元上进行的体内细胞外记录研究表明尼古丁具有直接抑制作用，但其作用机制尚不清楚。我们现在报告我们使用体外细胞内方法在浸没脑片制备中获得的研究结果，在该制备中，将烟碱型激动剂应用于大鼠背外侧隔区神经元，揭示了由钾电导增加介导的直接膜超极化。
