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, Feliksas F. Bukauskas

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


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.

Original languageEnglish (US)
Article number4667
JournalNature communications
StatePublished - Aug 19 2014
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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