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 journalArticle

29 Scopus citations

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.

Original languageEnglish (US)
Article number4667
JournalNature communications
Volume5
DOIs
StatePublished - Aug 19 2014

ASJC Scopus subject areas

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

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    Palacios-Prado, N., Chapuis, S., Panjkovich, A., Fregeac, J., Nagy, J. I., & Bukauskas, F. F. (2014). Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36. Nature communications, 5, [4667]. https://doi.org/10.1038/ncomms5667