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Proc Natl Acad Sci U S A
2008 Nov 04;10544:17169-74. doi: 10.1073/pnas.0804189105.
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Regulation of neuronal connexin-36 channels by pH.
González-Nieto D
,
Gómez-Hernández JM
,
Larrosa B
,
Gutiérrez C
,
Muñoz MD
,
Fasciani I
,
O'Brien J
,
Zappalà A
,
Cicirata F
,
Barrio LC
.
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Neurotransmission through electrical synapses plays an important role in the spike synchrony among neurons and oscillation of neuronal networks. Indeed, electrical transmission has been implicated in the hypersynchronous electrical activity of epilepsy. We have investigated the influence of intracellular pH on the strength of electrical coupling mediated by connexin36 (Cx36), the principal gap junction protein in the electrical synapses of vertebrates. In striking contrast to other connexin isoforms, the activity of Cx36 channels decreases following alkalosis rather than acidosis when it is expressed in Xenopus oocytes and N2A cells. This uncoupling of Cx36 channels upon alkalinization occurred in the vertebrate orthologues analyzed (human, mouse, chicken, perch, and skate). While intracellular acidification caused a mild or moderate increase in the junctional conductance of virtually all these channels, the coupling of the skate Cx35 channel was partially blocked by acidosis. The mutational analysis suggests that the Cx36 channels may contain two gating mechanisms operating with opposing sensitivity to pH. One gate, the dominant mechanism, closes for alkalosis and it probably involves an interaction between the C- and N-terminal domains, while a secondary acid sensing gate only causes minor, albeit saturating, changes in coupling following acidosis and alkalosis. Thus, we conclude that neuronal Cx36 channels undergo unique regulation by pH(i) since their activity is inhibited by alkalosis rather than acidosis. These data provide a novel basis to define the relevance and consequences of the pH-dependent modulation of Cx36 synapses under physiological and pathological conditions.
Barrio,
Gap junctions formed by connexins 26 and 32 alone and in combination are differently affected by applied voltage.
1991, Pubmed,
Xenbase
Barrio,
Gap junctions formed by connexins 26 and 32 alone and in combination are differently affected by applied voltage.
1991,
Pubmed
,
Xenbase
Belluardo,
Structure, chromosomal localization, and brain expression of human Cx36 gene.
1999,
Pubmed
Bennett,
Electrical coupling and neuronal synchronization in the Mammalian brain.
2004,
Pubmed
Blank,
Cytosolic pH measurements in single cardiac myocytes using carboxy-seminaphthorhodafluor-1.
1992,
Pubmed
Burr,
Calcium-dependent binding of calmodulin to neuronal gap junction proteins.
2005,
Pubmed
Chesler,
Regulation and modulation of pH in the brain.
2003,
Pubmed
Christie,
Connexin36 mediates spike synchrony in olfactory bulb glomeruli.
2005,
Pubmed
Condorelli,
Cloning of a new gap junction gene (Cx36) highly expressed in mammalian brain neurons.
1998,
Pubmed
Deans,
Synchronous activity of inhibitory networks in neocortex requires electrical synapses containing connexin36.
2001,
Pubmed
Duffy,
pH-dependent intramolecular binding and structure involving Cx43 cytoplasmic domains.
2002,
Pubmed
Duffy,
Regulation of connexin43 protein complexes by intracellular acidification.
2004,
Pubmed
Fukuda,
Gap junctions among dendrites of cortical GABAergic neurons establish a dense and widespread intercolumnar network.
2006,
Pubmed
González,
Species specificity of mammalian connexin-26 to form open voltage-gated hemichannels.
2006,
Pubmed
,
Xenbase
Güldenagel,
Visual transmission deficits in mice with targeted disruption of the gap junction gene connexin36.
2001,
Pubmed
Hampson,
Dopaminergic modulation of gap junction permeability between amacrine cells in mammalian retina.
1992,
Pubmed
Hamzei-Sichani,
Gap junctions on hippocampal mossy fiber axons demonstrated by thin-section electron microscopy and freeze fracture replica immunogold labeling.
2007,
Pubmed
Harris,
Emerging issues of connexin channels: biophysics fills the gap.
2001,
Pubmed
Hirst-Jensen,
Characterization of the pH-dependent interaction between the gap junction protein connexin43 carboxyl terminus and cytoplasmic loop domains.
2007,
Pubmed
Hormuzdi,
Impaired electrical signaling disrupts gamma frequency oscillations in connexin 36-deficient mice.
2001,
Pubmed
Landisman,
Electrical synapses in the thalamic reticular nucleus.
2002,
Pubmed
Li,
Neuronal connexin36 association with zonula occludens-1 protein (ZO-1) in mouse brain and interaction with the first PDZ domain of ZO-1.
2004,
Pubmed
Long,
Rhythmicity without synchrony in the electrically uncoupled inferior olive.
2002,
Pubmed
Long,
Electrical synapses coordinate activity in the suprachiasmatic nucleus.
2005,
Pubmed
Maier,
Reduction of high-frequency network oscillations (ripples) and pathological network discharges in hippocampal slices from connexin 36-deficient mice.
2002,
Pubmed
Martin,
Assembly of chimeric connexin-aequorin proteins into functional gap junction channels. Reporting intracellular and plasma membrane calcium environments.
1998,
Pubmed
,
Xenbase
Mas,
Association of the connexin36 gene with juvenile myoclonic epilepsy.
2004,
Pubmed
Morley,
Intramolecular interactions mediate pH regulation of connexin43 channels.
1996,
Pubmed
,
Xenbase
O'Brien,
Connexin 35: a gap-junctional protein expressed preferentially in the skate retina.
1996,
Pubmed
O'Brien,
Cloning and expression of two related connexins from the perch retina define a distinct subgroup of the connexin family.
1998,
Pubmed
,
Xenbase
Peracchia,
Chemical gating of gap junction channels; roles of calcium, pH and calmodulin.
2004,
Pubmed
Pereda,
Ca2+/calmodulin-dependent kinase II mediates simultaneous enhancement of gap-junctional conductance and glutamatergic transmission.
1998,
Pubmed
Rash,
Identification of connexin36 in gap junctions between neurons in rodent locus coeruleus.
2007,
Pubmed
Rash,
Immunogold evidence that neuronal gap junctions in adult rat brain and spinal cord contain connexin-36 but not connexin-32 or connexin-43.
2000,
Pubmed
Srinivas,
Functional properties of channels formed by the neuronal gap junction protein connexin36.
1999,
Pubmed
Swietach,
H+ ion activation and inactivation of the ventricular gap junction: a basis for spatial regulation of intracellular pH.
2007,
Pubmed
Söhl,
The murine gap junction gene connexin36 is highly expressed in mouse retina and regulated during brain development.
1998,
Pubmed
Söhl,
Expression and functions of neuronal gap junctions.
2005,
Pubmed
Teubner,
Functional expression of the murine connexin 36 gene coding for a neuron-specific gap junctional protein.
2000,
Pubmed
,
Xenbase
Traub,
Combined experimental/simulation studies of cellular and network mechanisms of epileptogenesis in vitro and in vivo.
2005,
Pubmed
Urschel,
Protein kinase A-mediated phosphorylation of connexin36 in mouse retina results in decreased gap junctional communication between AII amacrine cells.
2006,
Pubmed
Wellershaus,
A new conditional mouse mutant reveals specific expression and functions of connexin36 in neurons and pancreatic beta-cells.
2008,
Pubmed
White,
Functional characteristics of skate connexin35, a member of the gamma subfamily of connexins expressed in the vertebrate retina.
1999,
Pubmed
,
Xenbase
