Fisher J L, Dani J A
Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030-3498, USA.
Neuropharmacology. 2000 Oct;39(13):2756-69. doi: 10.1016/s0028-3908(00)00102-7.
Activation of presynaptic nicotinic acetylcholine receptors (nAChRs) can enhance the release of glutamate from synapses in hippocampal slices and cultures. In hippocampal cultures making autaptic connections, rapid application of a high concentration of nicotine activated presynaptic, postsynaptic, and somatic nAChRs, which consequently enhanced the amplitude of evoked excitatory postsynaptic currents (eEPSCs) mediated by glutamate receptors. The increased eEPSC amplitudes arose from enhanced glutamate release caused by presynaptic nAChRs (Radcliffe and Dani, 1998, Journal of Neuroscience 18, 7075). The same whole-cell nicotine applications that enhanced non-NMDA eEPSCs often decreased the NMDA-receptor component of the eEPSCs. Furthermore, whole-cell activation of nAChRs by nicotine selectively reduced the amplitude of the whole-cell NMDA-receptor currents without affecting the non-NMDA receptor currents. The inhibition by nicotine was prevented by the alpha7-specific antagonist, methyllycaconitine, and required the presence of extracellular Ca(2+). The calmodulin antagonist fluphenazine prevented inhibition of the NMDA-receptor current by nAChR activity, suggesting that a Ca(2+)-calmodulin-dependent process mediated the effect of nicotine. Our results indicate that activation of nAChRs can modulate glutamatergic synapses in several ways. Presynaptic nAChR activity enhances synaptic transmission by increasing transmitter release. Additionally, somatic or postsynaptic nAChRs can initiate a Ca(2+) signal that can act via calmodulin to reduce the responsiveness of NMDA receptors.
突触前烟碱型乙酰胆碱受体（nAChRs）的激活可增强海马脑片和培养物中突触处谷氨酸的释放。在形成自突触连接的海马培养物中，快速施加高浓度尼古丁可激活突触前、突触后和体细胞nAChRs，从而增强由谷氨酸受体介导的诱发兴奋性突触后电流（eEPSCs）的幅度。eEPSC幅度的增加源于突触前nAChRs引起的谷氨酸释放增强（拉德克利夫和达尼，1998年，《神经科学杂志》18卷，7075页）。增强非NMDA eEPSCs的相同全细胞尼古丁应用通常会降低eEPSCs的NMDA受体成分。此外，尼古丁对nAChRs的全细胞激活选择性地降低了全细胞NMDA受体电流的幅度，而不影响非NMDA受体电流。尼古丁的抑制作用可被α7特异性拮抗剂甲基lycaconitine阻止，且需要细胞外Ca(2+)的存在。钙调蛋白拮抗剂氟奋乃静可阻止nAChR活性对NMDA受体电流的抑制，表明Ca(2+) - 钙调蛋白依赖性过程介导了尼古丁的作用。我们的结果表明，nAChRs的激活可以通过多种方式调节谷氨酸能突触。突触前nAChR活性通过增加递质释放来增强突触传递。此外，体细胞或突触后nAChRs可以启动一个Ca(2+)信号，该信号可以通过钙调蛋白作用来降低NMDA受体的反应性。
