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

Author

Listed:
  • Nicolás Palacios-Prado

    (Albert Einstein College of Medicine
    Grass Laboratory, Marine Biological Laboratory)

  • 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)

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.

Suggested Citation

  • Nicolás Palacios-Prado & Sandrine Chapuis & Alejandro Panjkovich & Julien Fregeac & James I. Nagy & Feliksas F. Bukauskas, 2014. "Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5667
    DOI: 10.1038/ncomms5667
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    Cited by:

    1. Seu-Na Lee & Hwa-Jin Cho & Hyeongseop Jeong & Bumhan Ryu & Hyuk-Joon Lee & Minsoo Kim & Jejoong Yoo & Jae-Sung Woo & Hyung Ho Lee, 2023. "Cryo-EM structures of human Cx36/GJD2 neuronal gap junction channel," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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