Sargent Peter B
Department of Cell and Tissue Biology and the Neuroscience Graduate Program, University of California, San Francisco, San Francisco, California 94143-0640, USA.
J Neurosci. 2009 Mar 25;29(12):3749-59. doi: 10.1523/JNEUROSCI.5404-08.2009.
Rapid synaptic transmission at the calyciform synapse in the embryonic chicken ciliary ganglion is mediated by two classes of nicotinic receptors: those containing alpha3 subunits [alpha3-nicotinic ACh receptors (nAChRs)] and those containing alpha7 subunits (alpha7-nAChRs). alpha3-nAChRs and alpha7-nAChRs are differentially distributed on the cell surface; alpha3-nAChRs are concentrated at postsynaptic densities, whereas both alpha7-nAChRs and alpha3-nAChRs are found extrasynaptically on somatic spines. I explored the contribution of alpha3-nAChRs and alpha7-nAChRs to uniquantal responses, measured as mEPSCs, or as evoked responses under low release probability conditions. The contribution that each nAChR makes to uniquantal response shape was determined by blocking one nAChR type; pharmacologically isolated alpha7-nAChR responses were kinetically fast (rise time, 0.32 +/- 0.02 ms; decay time, 1.66 +/- 0.18 ms; mean +/- SD; n = 6 cells), whereas pharmacologically isolated alpha3-nAChR responses were slow (rise time, 1.28 +/- 0.35 ms; decay time, 6.71 +/- 1.46 ms; n = 8 cells). In the absence of antagonists, most cells (11 of 14) showed heterogeneity in the kinetics of uniquantal responses, with approximately 25% of events exhibiting fast, alpha7-nAChR-like kinetics and approximately 75% of events exhibiting the kinetics expected of coactivation of alpha7-nAChRs and alpha3-nAChRs. Cells rarely showed significant numbers of uniquantal responses with slow, alpha3-nAChR-like kinetics, which was unexpected given that alpha3-nAChRs alone are concentrated at postsynaptic densities. The only site where ACh quanta can activate both alpha3-nAChRs and alpha7-nAChRs readily is on the somatic spines, where alpha7-nAChRs and alpha3-nAChRs are present extrasynaptically. At the calyciform synapse, rapid synaptic transmission is mediated apparently without participation of ionotropic receptors concentrated at postsynaptic densities.
含α3亚基的受体[α3 - 烟碱型乙酰胆碱受体（nAChRs）]和含α7亚基的受体（α7 - nAChRs）。α3 - nAChRs和α7 - nAChRs在细胞表面呈差异分布；α3 - nAChRs集中于突触后致密区，而α7 - nAChRs和α3 - nAChRs在体棘突的突触外均有发现。我探究了α3 - nAChRs和α7 - nAChRs对以微小兴奋性突触后电流（mEPSCs）或低释放概率条件下的诱发反应来衡量的单量子反应的贡献。通过阻断一种nAChR类型来确定每种nAChR对单量子反应形状的贡献；药理学分离的α7 - nAChR反应在动力学上很快（上升时间，0.32±0.02毫秒；衰减时间，1.66±0.18毫秒；平均值±标准差；n = 6个细胞），而药理学分离的α3 - nAChR反应则较慢（上升时间，1.28±0.35毫秒；衰减时间，6.71±1.46毫秒；n = 8个细胞）。在没有拮抗剂的情况下，大多数细胞（14个中的11个）在单量子反应动力学上表现出异质性，约25%的事件呈现快速的、类似α7 - nAChR的动力学，约75%的事件呈现α7 - nAChRs和α3 - nAChRs共同激活预期的动力学。细胞很少显示出大量具有缓慢的、类似α3 - nAChR动力学的单量子反应，鉴于单独的α3 - nAChRs集中于突触后致密区，这是出乎意料的。乙酰胆碱量子能够轻易激活α3 - nAChRs和α7 - nAChRs的唯一部位是体棘突，α7 - nAChRs和α3 - nAChRs在其突触外存在。在杯状突触处，快速突触传递显然是在没有集中于突触后致密区的离子otropic受体参与的情况下介导的。
