title: Heterotypic gap junctions at glutamatergic mixed synapses are abundant in goldfish brain.
abstract: 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.
authors.affiliation: 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. Electronic address: john.rash@colostate.edu.
authors.forename: J E
authors.initials: JE
authors.lastname: Rash
authors.affiliation: Max Planck Florida Institute for Neuroscience, Jupiter, FL, United States.
authors.forename: N
authors.initials: N
authors.lastname: Kamasawa
authors.affiliation: Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
authors.forename: K G
authors.initials: KG
authors.lastname: Vanderpool
authors.affiliation: Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, United States.
authors.forename: T
authors.initials: T
authors.lastname: Yasumura
authors.affiliation: Department of Ophthalmology and Visual Science, University of Texas Health Science Center, Houston, TX, United States.
authors.forename: J
authors.initials: J
authors.lastname: O'Brien
authors.affiliation: Dominick Purpura Department of Neurosciences, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, United States.
authors.forename: S
authors.initials: S
authors.lastname: Nannapaneni
authors.affiliation: Dominick Purpura Department of Neurosciences, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, United States.
authors.forename: A E
authors.initials: AE
authors.lastname: Pereda
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: J I
authors.initials: JI
authors.lastname: Nagy
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D029941:Fish Proteins / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006054:Goldfish / Q000378:metabolism*; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D013569:Synapses / Q000378:metabolism*
chemical_list: D029941:Fish Proteins; D018698:Glutamic Acid
keywords: connexin34.7; connexin35; freeze-fracture replica immunogold labeling (FRIL); gap junctions; immunofluorescence microscopy