Rash J E, Kamasawa N, Vanderpool K G, Yasumura T, O'Brien J, Nannapaneni S, Pereda A E, Nagy J I
Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, United States; Program in Molecular, Cellular and Integrative Neurosciences, Colorado State University, Fort Collins, CO, United States.
Max Planck Florida Institute for Neuroscience, Jupiter, FL, United States.
Neuroscience. 2015 Jan 29;285:166-93. doi: 10.1016/j.neuroscience.2014.10.057. Epub 2014 Nov 4.
Gap junctions provide for direct intercellular electrical and metabolic coupling. The abundance of gap junctions at "large myelinated club ending (LMCE)" synapses on Mauthner cells (M-cells) of the teleost brain provided a convenient model to correlate anatomical and physiological properties of electrical synapses. There, presynaptic action potentials were found to evoke short-latency electrical "pre-potentials" immediately preceding their accompanying glutamate-induced depolarizations, making these the first unambiguously identified "mixed" (i.e., chemical plus electrical) synapses in the vertebrate CNS. We recently showed that gap junctions at these synapses exhibit asymmetric electrical resistance (i.e., electrical rectification), which we correlated with total molecular asymmetry of connexin composition in their apposing gap junction hemiplaques, with connexin35 (Cx35) restricted to axon terminal hemiplaques and connexin34.7 (Cx34.7) restricted to apposing M-cell plasma membranes. We now show that similarly heterotypic neuronal gap junctions are abundant throughout goldfish brain, with labeling exclusively for Cx35 in presynaptic hemiplaques and exclusively for Cx34.7 in postsynaptic hemiplaques. Moreover, the vast majority of these asymmetric gap junctions occur at glutamatergic axon terminals. The widespread distribution of heterotypic gap junctions at glutamatergic mixed synapses throughout goldfish brain and spinal cord implies that pre- vs. postsynaptic asymmetry at electrical synapses evolved early in the chordate lineage. We propose that the advantages of the molecular and functional asymmetry of connexins at electrical synapses that are so prominently expressed in the teleost CNS are unlikely to have been abandoned in higher vertebrates. However, to create asymmetric coupling in mammals, where most gap junctions are composed of connexin36 (Cx36) on both sides, would require some other mechanism, such as differential phosphorylation of connexins on opposite sides of the same gap junction or on asymmetric differences in the complement of their scaffolding and regulatory proteins.
缝隙连接实现了细胞间的直接电偶联和代谢偶联。硬骨鱼脑内莫氏细胞（M细胞）上“大型有髓终末（LMCE）”突触处丰富的缝隙连接，为关联电突触的解剖学和生理学特性提供了一个便利的模型。在那里，发现突触前动作电位会在其伴随的谷氨酸诱导的去极化之前立即引发短潜伏期的电“预电位”，这使得这些突触成为脊椎动物中枢神经系统中首个被明确鉴定的“混合”（即化学性加电性）突触。我们最近表明，这些突触处的缝隙连接表现出不对称电阻（即电整流），我们将其与相邻缝隙连接半斑中连接蛋白组成的整体分子不对称性相关联，其中连接蛋白35（Cx35）局限于轴突终末半斑，而连接蛋白34.7（Cx34.7）局限于相对的M细胞质膜。我们现在表明，类似的异型神经元缝隙连接在金鱼脑中广泛存在，突触前半斑仅标记Cx35，突触后半斑仅标记Cx34.7。此外，这些不对称缝隙连接绝大多数出现在谷氨酸能轴突终末。异型缝隙连接在金鱼脑和脊髓中谷氨酸能混合突触处的广泛分布意味着，电突触处突触前与突触后的不对称性在脊索动物谱系中很早就已演化形成。我们提出，硬骨鱼中枢神经系统中如此显著表达的电突触处连接蛋白的分子和功能不对称性的优势，在高等脊椎动物中不太可能被舍弃。然而，在哺乳动物中，大多数缝隙连接两侧均由连接蛋白36（Cx36）组成，要产生不对称偶联将需要一些其他机制，例如同一缝隙连接相对两侧连接蛋白的差异磷酸化，或者其支架蛋白和调节蛋白组成上的不对称差异。
