Intracellular magnesium-dependent modulation of gap junction channels formed by neuronal connexin36

Nicolás Palacios-Prado, Gregory Hoge, Alina Marandykina, Lina Rimkute, Sandrine Chapuis, Nerijus Paulauskas, Vytenis A. Skeberdis, John O'Brien, Alberto E. Pereda, Michael V.L. Bennett, Feliksas F. Bukauskas

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Abstract

Gap junction (GJ) channels composed of Connexin36 (Cx36) are widely expressed in the mammalian CNS and form electrical synapses between neurons. Here we describe a novel modulatory mechanism of Cx36 GJ channels dependent on intracellular free magnesium ([Mg2+]i). We examined junctional conductance (gj) and its dependence on transjunctional voltage (Vj) at different [Mg2+]i in cultures of HeLa or N2A cells expressing Cx36. We found that Cx36 GJs are partially inhibited at resting [Mg2+]i. Thus, gj can be augmented or reduced by lowering or increasing [Mg2+]i, respectively. Similar changes in gj and Vj-gating were observed using MgATP or K2ATP in pipette solutions, which increases or decreases [Mg2+]i, respectively. Changes in phosphorylation of Cx36 or in intracellular free calcium concentration were not involved in the observed Mg2+-dependent modulation of gj. Magnesium ions permeate the channel and transjunctional asymmetry in [Mg2+]i resulted in asymmetric Vj-gating. The gj of GJs formed of Cx26, Cx32, Cx43, Cx45, and Cx47 was also reduced by increasing [Mg2+]i, but was not increased by lowering [Mg2+]i; single-channel conductance did not change. We showed that [Mg2+]i affects both open probability and the number of functional channels, likely through binding in the channel lumen. Finally, we showed that Cx36-containing electrical synapses between neurons of the trigeminal mesencephalic nucleus in rat brain slices are similarly affected by changes in [Mg2+]i. Thus, this novel modulatory mechanism could underlie changes in neuronal synchronization under conditions in which ATP levels, and consequently [Mg2+]i, are modified.

Original languageEnglish (US)
Pages (from-to)4741-4753
Number of pages13
JournalJournal of Neuroscience
Volume33
Issue number11
DOIs
StatePublished - Mar 13 2013

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Palacios-Prado, N., Hoge, G., Marandykina, A., Rimkute, L., Chapuis, S., Paulauskas, N., Skeberdis, V. A., O'Brien, J., Pereda, A. E., Bennett, M. V. L., & Bukauskas, F. F. (2013). Intracellular magnesium-dependent modulation of gap junction channels formed by neuronal connexin36. Journal of Neuroscience, 33(11), 4741-4753. https://doi.org/10.1523/JNEUROSCI.2825-12.2013