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- Title
Intracellular Magnesium-Dependent Modulation of Gap Junction Channels Formed by Neuronal Connexin36.
- Authors
Palacios-Prado, Nicolás; Hoge, Gregory; Marandykina, Alina; Rimkute, Lina; Chapuis, Sandrine; Paulauskas, Nerijus; Skeberdis, Vytenis A.; O'Brien, John; Pereda, Alberto E.; Bennett, Michael V. L.; Bukauskas, Feliksas F.
- 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 (V:) 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 ingj 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+]i -dependent modulation ofgj. Magnesium ions permeate the channel and trans-junctional asymmetry in [Mg2+]i( resulted in asymmetric legating. 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 simi-larly 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.
- Subjects
INTRACELLULAR calcium; GAP junctions (Cell biology); CONNEXINS; SYNAPSES; ADENOSINE triphosphate; MAGNESIUM ions
- Publication
Journal of Neuroscience, 2013, Vol 33, Issue 11, p4741
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2825-12.2013