Articulo
Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36
Nature Communications
Registro en:
72111120
72111120
Autor
Palacios-Prado, Nicolas
Institución
Resumen
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.