| First Author | Palacios-Prado N | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 4667 | PubMed ID | 25135336 |
| Mgi Jnum | J:250775 | Mgi Id | MGI:6099691 |
| Doi | 10.1038/ncomms5667 | Citation | Palacios-Prado N, et al. (2014) Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36. Nat Commun 5:4667 |
| abstractText | 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. |
