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Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36

Nicolás Palacios-Prado (), Sandrine Chapuis, Alejandro Panjkovich, Julien Fregeac, James I. Nagy and Feliksas F. Bukauskas ()
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Nicolás Palacios-Prado: Albert Einstein College of Medicine
Sandrine Chapuis: Albert Einstein College of Medicine
Alejandro Panjkovich: European Molecular Biology Laboratory, Hamburg Outstation
Julien Fregeac: Albert Einstein College of Medicine
James I. Nagy: University of Manitoba
Feliksas F. Bukauskas: Albert Einstein College of Medicine

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: 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 ([Mg2+]i). Chimeragenesis demonstrates that the first extracellular loop of Cx36 contains a Mg2+-sensitive domain, and site-directed mutagenesis shows that the pore-lining residue D47 is critical in determining high Mg2+-sensitivity. Single-channel analysis of Mg2+-sensitive chimeras and mutants reveals that [Mg2+]i controls the strength of electrical coupling mostly via gating mechanisms. In addition, asymmetric transjunctional [Mg2+]i induces strong instantaneous rectification, providing a novel mechanism for electrical rectification in homotypic Cx36 GJs. We suggest that Mg2+-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 [Mg2+]i.

Date: 2014
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DOI: 10.1038/ncomms5667

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