Girod R, Barazangi N, McGehee D, Role L W
Department of Anatomy and Cell Biology in The Center for Neurobiology and Behavior, Columbia University, College of Physicians and Surgeons, 1051 Riverside Dr., P.I. Annex 807, New York, NY, 10032, USA.
Neuropharmacology. 2000 Oct;39(13):2715-25. doi: 10.1016/s0028-3908(00)00145-3.
The profiles of presynaptic facilitation of glutamate release as elicited by nicotine and acetylcholine were compared in two limbic pathways recapitulated in vitro. At synapses of medial habenula (MHN) and interpeduncular nucleus (IPN) neurons, application of nicotine increased the frequency of TTX-resistant, spontaneous postsynaptic currents (SSCs) by an average of 5-fold. In contrast, the average increase in SSC frequency elicited by nicotine was more than 120 fold at synapses of olfactory bulb (OB) and amygdala neurons. At both preparations, pulses of ACh caused presynaptic facilitation that lasted longer than that elicited by nicotine. The subunit composition of presynaptic nAChRs may contribute to the different profiles of facilitation observed. The large magnitude, fast kinetics, and alpha-bungarotoxin sensitivity of facilitation observed at OB-amygdala synapses is consistent with participation of alpha7-type nAChRs. As subunit-selective deletion of alpha5 or alpha7 altered the profile of nicotine-elicited facilitation at MHN-IPN synapses, presynaptic nAChRs at MHN-IPN synapses appear to be more complex. Such heteromeric combinations of nAChRs may contribute to the lower magnitude and slower kinetics of presynaptic facilitation at MHN-IPN synapses. Calcium influx through either voltage-gated calcium channels or directly through presynaptic alpha7-containing nAChRs is sufficient to support nicotine-elicited facilitation of glutamate release. Resultant increases in intracellular calcium may further modulate presynaptic nAChR activity in a subunit-composition dependent manner.
在体外重现的两条边缘通路中，比较了尼古丁和乙酰胆碱引发的谷氨酸释放的突触前易化情况。在内侧缰核（MHN）和脚间核（IPN）神经元的突触处，应用尼古丁使对河豚毒素（TTX）不敏感的自发性突触后电流（SSCs）频率平均增加了5倍。相比之下，在嗅球（OB）和杏仁核神经元的突触处，尼古丁引发的SSC频率平均增加超过120倍。在这两种标本中，乙酰胆碱脉冲引起的突触前易化持续时间比尼古丁引发的更长。突触前烟碱型乙酰胆碱受体（nAChRs）的亚基组成可能导致观察到的不同易化情况。在OB-杏仁核突触处观察到的易化具有幅度大、动力学快和对α-银环蛇毒素敏感的特点，这与α7型nAChRs的参与一致。由于α5或α7的亚基选择性缺失改变了MHN-IPN突触处尼古丁引发的易化情况，因此MHN-IPN突触处的突触前nAChRs似乎更为复杂。这种nAChRs的异聚体组合可能导致MHN-IPN突触处突触前易化的幅度较低和动力学较慢。通过电压门控钙通道或直接通过突触前含α7的nAChRs的钙内流足以支持尼古丁引发的谷氨酸释放易化。由此导致的细胞内钙增加可能进一步以亚基组成依赖的方式调节突触前nAChR活性。
