title: Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36.
abstract: Neuronal gap junction (GJ) channels composed of connexin36 (Cx36) play an important role in neuronal synchronization and network dynamics. Here we show that Cx36-containing electrical synapses between inhibitory neurons of the thalamic reticular nucleus are bidirectionally modulated by changes in intracellular free magnesium concentration ([Mg(2+)]i). Chimeragenesis demonstrates that the first extracellular loop of Cx36 contains a Mg(2+)-sensitive domain, and site-directed mutagenesis shows that the pore-lining residue D47 is critical in determining high Mg(2+)-sensitivity. Single-channel analysis of Mg(2+)-sensitive chimeras and mutants reveals that [Mg(2+)]i controls the strength of electrical coupling mostly via gating mechanisms. In addition, asymmetric transjunctional [Mg(2+)]i induces strong instantaneous rectification, providing a novel mechanism for electrical rectification in homotypic Cx36 GJs. We suggest that Mg(2+)-dependent synaptic plasticity of Cx36-containing electrical synapses could underlie neuronal circuit reconfiguration via changes in brain energy metabolism that affects neuronal levels of intracellular ATP and [Mg(2+)]i.
authors.affiliation: 1] Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA [2] Grass Laboratory, Marine Biological Laboratory, Woods Hole, Woods Hole, Massachusetts 02543, USA.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Palacios-Prado
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Chapuis
authors.affiliation: European Molecular Biology Laboratory, Hamburg Outstation, 22603 Hamburg, Germany.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Panjkovich
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Julien
authors.initials: J
authors.lastname: Fregeac
authors.affiliation: Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0J9.
authors.forename: James I
authors.initials: JI
authors.lastname: Nagy
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Feliksas F
authors.initials: FF
authors.lastname: Bukauskas
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D000941:Antigens / Q000502:physiology; D018031:Connexin 43 / Q000502:physiology; D017630:Connexins / Q000737:chemistry* / Q000502:physiology*; D054351:Electrical Synapses / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D008274:Magnesium / Q000502:physiology*; D008297:Male; D051379:Mice; D023421:Models, Animal; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D013787:Thalamic Nuclei / Q000502:physiology*; D000097004:Gap Junction delta-2 Protein
chemical_list: D000255:Adenosine Triphosphate; D000941:Antigens; D018031:Connexin 43; D017630:Connexins; D008274:Magnesium; D000097004:Gap Junction delta-2 Protein; C042182:D47 antigen