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Nat Commun. 2014 Aug 19;5:4667. doi: 10.1038/ncomms5667.

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

Author information

1
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.
2
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
3
European Molecular Biology Laboratory, Hamburg Outstation, 22603 Hamburg, Germany.
4
Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0J9.

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.

PMID:
25135336
PMCID:
PMC4142521
DOI:
10.1038/ncomms5667
[Indexed for MEDLINE]
Free PMC Article

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