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Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36
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Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36
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Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36
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Journal Article
Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36
2014
Overview
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
.
Electrical synaptic transmission is known to be modulated by intracellular magnesium. Here, Palacios-Prado
et al.
show that electrical synapses formed by connexin36 in the thalamic reticular nucleus are bidirectionally modulated by changes in magnesium concentration via pore-lining sensitive domains.
Publisher
Nature Publishing Group UK,Nature Publishing Group
