Gap junction wiring: a `new' principle in cell-to-cell communication in the nervous system?

doi:10.1016/S0165-0173(97)00031-3

Brain Research Reviews

Volume 26, Issues 2–3, May 1998, Pages 176-183

https://doi.org/10.1016/S0165-0173(97)00031-3 Get rights and content

Abstract

This review gives an updated excerpt of recent advances in our understanding of brain gap junctions. It starts with a brief description of the principle molecular composition of gap junctions before specific issues concerning brain tissues are addressed. The following questions and matters are subjected to a detailed analysis: First, why are there so many gap junctions in the brain? Second, what is the functional significance of the cellular diversity of brain gap junctions? Third, how do astrocytic gap junctions mediate intercellular volume transmission (IVT), and what does IVT mean for glial–neuronal interaction? Fourth, how frequent are interneuronal gap junctions; and what is their functional significance in brain development and in interrelated chemical–electrotonic transmission at mixed synapses.

Section snippets

Molecular diversity of gap junction channels

Understanding of the properties and functions of gap junctions in neural tissues requires a basic knowledge of their molecular composition. The idea that gap junctions constitute a uniform type of intercellular channels with little diversity and no selectivity for other partners or permeants is largely challenged by recent molecular work. It is now widely accepted that gap junction proteins are encoded by a gene family from which thirteen members have been cloned in mammals 5, 20, 55and at

Neuronal coupling

Evidence that neurons display a considerable degree of coupling via gap junctions is also accruing. At least in immature neuroblasts and postnatal neurons extensive gap junction mediated intercellular coupling has been documented 27, 36. In embryonic brains cohorts of neuroblasts have been described which exhibit transient but coordinated elevations of intracellular Ca²⁺ and the idea has been put forward that such cohorts of coupled neuroblasts represent assemblies of cells primed for concerted

Acknowledgements

Most of the research enclosed in this review was substantially supported by the Deutsche Forschungsgemeinschaft. I thank my collaborator and friend David Spray for his helpful comments on the manuscript.

References (56)

M.V.L. Bennett et al.
Gap junctions: new tools, new answers, new questions
Neuron
(1991)
G. Dahl et al.
Attempts to define functional domains of gap junction proteins with synthetic peptides
Biophys. J.
(1994)
R. Dermietzel et al.
Gap Junctions in the brain: where, what type, how many and why?
Trends Neurosci.
(1993)
J.-A. Haefliger et al.
Four novel members of the connexin family of gap junction proteins. [Molecular cloning, expression, and chromosome mapping]
J. Biol. Chem.
(1992)
K. Jungermann et al.
Regulation of liver metabolism by the hepatic nerves
Adv. Enzyme Regul.
(1987)
K. Kandler et al.
Neuronal coupling and uncoupling in the developing nervous system
Curr. Opin. Neurobiol.
(1995)
I.M. Neuhaus et al.
Use of alternate promoters for tissue-specific expression of the gene coding for connexin 32
Gene
(1995)
M.J. Sanderson et al.
Mechanisms and function of intercellular calcium signaling
Mol. Cell. Endocrinol.
(1994)
K. Stauffer
The gap junction proteins beta 1-connexin (connexin32) and beta-2 connexin (connexin26) can form heteromeric hemichannels
J. Biol. Chem.
(1995)
L.F. Agnati et al.
A correlation analysis of the regional distribution of central enkephalin and beta-endorphin immunoreactive terminals and of opiate receptors in adult and old male rats. Evidence for the existence of two main types of communication in the central nervous system: the volume transmission and the wiring transmission
Acta Physiol. Scand.
(1986)

M.V. Bennett et al.

Gap junctions, electrotonic coupling, and intercellular communication

Neurosci. Res. Program Bull.

(1978)

M.V.L. Bennett, Gap junctions as electrical synapses. In: D.C. Spray, R. Dermietzel (Eds.), Gap Junctions in the...

E.C. Beyer

Gap Junctions, Intern. Rev. Cytol.

(1993)

A.C. Charles et al.

Mechanisms of intercellular calcium signaling in glial cells studied with Dantrolene and Thapsigargin

Glia

(1993)

A.H. Cornell-Bell et al.

Glutamate induces calcium waves in cultured astrocytes: Long-range glial signaling

Science

(1991)

R. Dermietzel et al.

Differential expression of three gap junction proteins in developing and mature brain tissue

Proc. Natl. Acad. Sci. USA

(1989)

R. Dermietzel et al.

The gap junction family: structure, function and chemistry

Anat. Embryol.

(1990)

R. Dermietzel, Molecular diversity and plasticity of gap junctions in the nervous system. In: D.C. Spray, R. Dermietzel...

F.E. Dudek et al.

Role of electrical interactions in synchronization of epileptiform bursts

Adv. Neurol.

(1986)

C. Elfgang et al.

Specific permeability and selective formation of gap junction channels in connexin-transfected HeLa cells

J. Cell Biol.

(1995)

S. Finkbeiner, Calcium waves in astrocytes-filling in the gaps, Neuron (1992)...

J.L. Flagg-Newton et al.

Cell junction and cyclic AMP: I. Upregulation of junctional membrane permeability and junctional membrane particles by administration of cyclic nucleotide or phosphodiesterase inhibitor

J. Membr. Biol.

(1981)

J.L. Flagg-Newton et al.

Cell junction and cyclic AMP: II. Modulations of junctional membrane permeability, dependent on serum and cell density

J. Membr. Biol.

(1981)

E.J. Furshpan et al.

Transmission at the giant motor motor synapses of the cray fish

J. Physiol.

(1959)

C. Giaume et al.

Endothelins inhibit junctional permeability in cultured mouse astrocytes

Eur. J. Neurosci.

(1992)

E.C.G.M. Hampson et al.

Dopaminergic modulation of gap junction permeability between amacrine cells in mammalian retina

J. Neurosci.

(1992)

E.C. Hampson et al.

pH-gated dopaminergic modulation of horizontal cell gap junctions in mammalian retina

Proc. R. Soc. Lond. B. Biol. Sci.

(1994)

H. Kettenmann, B.R. Ransom, Neuroglia, Oxford University Press Oxford, New York,...

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Remarkably, GJ coupling with an exchange of metabolites closely resonates with direct cell-cell connections in cellular colonies bound via cytoplasmic bridges, as discussed earlier. Currently, a large family of channel-forming GJ proteins (connexin (Cx) and their homologs) have been identified and cloned from various tissue types (Beyer & Berthoud, 2017, 2018; Dermietzel, 1998), with over 20 Cx genes identified in rodents and humans, of which 5 are highly expressed in the mammalian central nervous system (Elias & Kriegstein, 2008). In stark contrast to intrinsically asymmetric and stochastic transmission at chemical synapses, signal exchange at electrical synapses is highly reliable and generally is symmetrical (i.e., bidirectional), although examples of rectifying contacts have also been documented (Oh, Rubin, Bennett, Verselis, & Bargiello, 1999; Sotelo & Korn, 1978).
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Quantum states in microtubules in one neuron can, we propose, extend by entanglement and tunneling through gap junctions to microtubules in adjacent neurons (including inter-neurons), potentially extending to brain-wide syncytia. Beginning in 1998, evidence began to show that gamma synchrony, the best measurable correlate of consciousness, depended on gap junctions, particularly dendritic–dendritic gap junctions [49–54]. To account for the distinction between conscious activities and non-conscious ‘auto-pilot’ activities, and the fact that consciousness can occur in various brain regions, Hameroff [22] developed the ‘Conscious pilot’ model in which syncytial zones of dendritic gamma synchrony move around the brain, regulated by gap junction openings and closings, in turn regulated by microtubules.
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¹: Published on the World Wide Web on 4 November 1997.

View full text

Gap junction wiring: a `new' principle in cell-to-cell communication in the nervous system?1

Abstract

Section snippets

Molecular diversity of gap junction channels

Neuronal coupling

Acknowledgements

Neuron

Biophys. J.

Trends Neurosci.

J. Biol. Chem.

Adv. Enzyme Regul.

Curr. Opin. Neurobiol.

Gene

Mol. Cell. Endocrinol.

J. Biol. Chem.

Acta Physiol. Scand.

Gap junctions, electrotonic coupling, and intercellular communication

Neurosci. Res. Program Bull.

Gap Junctions, Intern. Rev. Cytol.

Mechanisms of intercellular calcium signaling in glial cells studied with Dantrolene and Thapsigargin

Glia

Glutamate induces calcium waves in cultured astrocytes: Long-range glial signaling

Science

Differential expression of three gap junction proteins in developing and mature brain tissue

Proc. Natl. Acad. Sci. USA

The gap junction family: structure, function and chemistry

Anat. Embryol.

Role of electrical interactions in synchronization of epileptiform bursts

Adv. Neurol.

Specific permeability and selective formation of gap junction channels in connexin-transfected HeLa cells

J. Cell Biol.

Cell junction and cyclic AMP: I. Upregulation of junctional membrane permeability and junctional membrane particles by administration of cyclic nucleotide or phosphodiesterase inhibitor

J. Membr. Biol.

Cell junction and cyclic AMP: II. Modulations of junctional membrane permeability, dependent on serum and cell density

J. Membr. Biol.

Transmission at the giant motor motor synapses of the cray fish

J. Physiol.

Endothelins inhibit junctional permeability in cultured mouse astrocytes

Eur. J. Neurosci.

Dopaminergic modulation of gap junction permeability between amacrine cells in mammalian retina

J. Neurosci.

pH-gated dopaminergic modulation of horizontal cell gap junctions in mammalian retina

Proc. R. Soc. Lond. B. Biol. Sci.

Gap junction wiring: a `new' principle in cell-to-cell communication in the nervous system?¹