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Bioelectricity  ·  Article

Gap junctions

Gap junctions are membrane channels that pass small molecules and ions directly between neighbouring cells.1 They are built from connexin proteins in vertebrates and innexins in invertebrates.3 Because voltage can cross them, cells can sense the membrane potential of their neighbours.1 In the held texts they matter because blocking them changes the body plan that a regenerating or developing tissue builds.2

Earliest held
2011, Carneiro K, Donnet C, Rejtar…
Most discussed in
Cell Systems Bioelectricity: How Different…, 2021
In the library
249 passages in 43 works
Rewritten
2026-10-03
18501875190019251950197520002025Lobo D, Beane WS, Levin M, 20121Lobo D, Beane WS, Levin M, 20122Funk RH, 20153Blackiston DJ, Anderson GM, Rahman N…, 20154Emmons-Bell M, Durant F, Hammelman J…, 20155Neuhof M, Levin M, Rechavi O, 20166Riol A, Cervera J, Levin M, Mafe S, 20217Silic MR, Zhang G, 20238
01

Structure and naming

Silic and Zhang (2023) describe a gap junction as six connexin subunits on one cell joined to six on the adjacent cell.8 They note that the channel is passive and runs down an electrochemical gradient, so it does not rely on ATP-like ion pumps.8 A junction of one isoform is homomeric, and a mixed one is heteromeric.8 Funk (2015) names connexins in vertebrates and innexins in invertebrates.3 Funk adds that innexins were renamed pannexins after they were also found in vertebrates.3 Silic and Zhang list connexins and pannexins for vertebrates and innexins for invertebrates.8

02

Planarian experiments

Lobo, Beane and Levin (2012) report that isolating cells from gap junction communication with other regions of the worm leads to secondary heads.2 They cite both octanol, a long-chain alcohol, and RNAi against planarian innexins.2 Neuhof, Levin and Rechavi (2016) describe RNAi against three innexins giving a two-headed worm, and say a 2-day octanol exposure gives the same result.6 They add that octanol leaves the tissue within 24 hours, unlike RNAi.6 Emmons-Bell and colleagues (2015) judge that 8-OH only partly blocks the junctions, which fits a stochastic phenotype.5 They cannot rule out other targets, and they note that innexin proteins can compensate for one another.5

03

Carrying voltage and signals

Lobo and colleagues state that voltage gradients can be transmitted and altered through gap junctions, so cells can sense the potential of their neighbours.1 Funk (2015) adds that groups of cells exchange ions, second messengers and metabolites through them, which builds membrane potential gradients quickly.3 In Blackiston and colleagues (2015), ectopic eyes hyperinnervated hosts in ivermectin, and the dominant negative connexin construct H7 brought innervation back to control levels.4 They conclude that gap junction communication is essential for this response to depolarization.4

04

Connexin identity in models

Riol, Cervera, Levin and Mafe (2021) simulated cell aggregates whose junctions contain different connexins. They report that cells may express different connexins to regionalize membrane potentials.7 They also report that raising connectivity does not necessarily normalize bioelectric state.7 Two regions can stay differently polarized if each is well connected inside and poorly connected to the other.7 On that basis they suggest that lowering specific connexin levels could suit some cases and stages.7 The work is computational.

SourcesEach quotation was checked word for word against the passage it opens.
  1. Gap junctions are membrane channels that dynamically allow for the direct transmission of small molecules and ions between cellsLobo D, Beane WS, Levin M, 2012 · Modeling planarian regeneration: a primer for reverse-engineering the worm · open at passage 17
  2. isolating cells from gap junction-based communication with other regions of the worm leads to inappropriate generation of secondary headsLobo D, Beane WS, Levin M, 2012 · Modeling planarian regeneration: a primer for reverse-engineering the worm · open at passage 27
  3. These membrane proteins are called connexins in vertebrates and innexins in invertebrates. The innexins have recently be renamed pannexins, because they were recently also found in vertebrates.Funk RH, 2015 · Endogenous electric fields as guiding cue for cell migration · open at passage 19
  4. These results confirm those of chemical gap junction inhibition, and show that gap junction communication is essential for ectopic eyes to hyperinnervate hosts in response to membrane depolarization.Blackiston DJ, Anderson GM, Rahman N, Bieck C, Levin M, 2015 · A novel method for inducing nerve growth via modulation of host resting… · open at passage 35
  5. The space of all possible combinations of different innexin-RNAi’s that would have to be tried simultaneously is enormous, because GJ proteins can often compensate for one another.Emmons-Bell M, Durant F, Hammelman J, Bessonov N, Volpert…, 2015 · Gap Junctional Blockade Stochastically Induces Different Species-Specific Head… · open at passage 34
  6. The same result can be achieved by a transient (2-day) inhibition of gap junction communication using a blocker such as octanol (Nogi and Levin, 2005).Neuhof M, Levin M, Rechavi O, 2016 · Vertically- and horizontally-transmitted memories - the fading boundaries… · open at passage 36
  7. We computationally showed that cells may express different connexin proteins as a way to regionalize membrane potentials in multicellular aggregatesRiol A, Cervera J, Levin M, Mafe S, 2021 · Cell Systems Bioelectricity: How Different Intercellular Gap Junctions Could… · open at passage 36
  8. Each gap junction comprises six connexin subunits on one cell that oligomerize with another six connexins on an adjacent cell.Silic MR, Zhang G, 2023 · Bioelectricity in Developmental Patterning and Size Control: Evidence and… · open at passage 14
Linked ideas
Lobo and Funk say voltage gradients pass through gap junctions, so cells can sense neighbours' membrane potential; Riol models how connexin type regionalizes it.
Gap junction coupling is the route by which voltage and signal patterns are shared across cell groups, as in planarian polarity after junction blockade.
Manicka and Levin pair channels and pumps with gap junctions in cell networks; George and Bates link connexin43 mutations to shorter zebrafish fins.
Chernet, Fields and Levin found that disrupting gap junctional communication suppressed oncogene effects, contrary to the view that lost coupling marks incipient cancer.
Emmons-Bell et al. show gap-junction coupling changes persisting after a brief block, a candidate physical basis for the stored pattern memory.
Funk says open gap junction networks carry long-range information that could produce field-like patterning comparable to physiological gradients.
Left-right asymmetrypart of / contains
Carneiro et al. describe serotonin moving through gap-junctional paths at cleavage stages as setting asymmetry upstream of Nodal-related 1 in Xenopus.
Emmons-Bell et al. use gap junction blockade to alter planarian morphology and neoblast distribution.
Basal cognitionrelated to
Levin (2022) lists gap junctions and bioelectricity among the keywords tying basal cognition to regeneration and synthetic morphology.
Scale of the selfpart of / contains
Levin (2022) uses gap junctional coupling as the case study for how the self boundary expands or contracts.
Serotonin passes through gap junctions and, per Durant et al., also regulates them, suggesting feedback loops between the two.
Regenerationrelated to
Gap junctions are a mechanism of regeneration control: blocking them with octanol/8-OH in planaria alters regenerated head shape or yields double-headed animals, and they carry long-range axis information to the blastema.
Gap junctions propagate Vmem states across cell networks (isopotential fields); depolarization/hyperpolarization are those states. Both gap junction blockade and depolarization yield double-headed planarians; GJC modulates hyperpolarization's effect on tumors.
Passages show gap junctions as a mechanism in bioelectric patterning experiments (tumorigenesis, planarian polarity, regeneration), outcomes stochastic under blockade; none explicitly discusses determinism, so the link is indirect.
McMillen and Levin list the sharing of cellular memories and shared stress through gap junctions as a way higher-order individuals are established.
Bayliss's structural discontinuity of neurones concerns contact between cells, with physiological continuity across it.
Polarityrelated to
Blocking gap junctions in planaria gives secondary heads, so junction communication is needed for head-tail polarity.
Passages tie them via gap junctions in homeostatic plasticity (pancreatic beta-cell insulin control) and planarian anatomical homeostasis regulated by bioelectric signaling through ion channels and gap junctions (electrical synapses).
Where it is discussedPassages matching gap junction, gap junctional, connexin, innexin
2021Cell Systems Bioelectricity: How Different Intercellular Gap Junctions Could… · Riol A, Cervera J, Levin M, Mafe S25
2015Gap Junctional Blockade Stochastically Induces Different Species-Specific Head… · Emmons-Bell M, Durant F, Hammelman J…22
2014Long-range gap junctional signaling controls oncogene-mediated tumorigenesis in… · Chernet BT, Fields C, Levin M16
2022Technological Approach to Mind Everywhere: An Experimentally-Grounded Framework… · Levin M15
2016Exploring Instructive Physiological Signaling with the Bioelectric Tissue… · Pietak A, Levin M13
2019Modeling somatic computation with non-neural bioelectric networks · Manicka S, Levin M10
2015Endogenous electric fields as guiding cue for cell migration · Funk RH9
2023Bioelectricity in Developmental Patterning and Size Control: Evidence and… · Silic MR, Zhang G8
2016Vertically- and horizontally-transmitted memories - the fading boundaries… · Neuhof M, Levin M, Rechavi O8
2021Beyond Neurons: Long Distance Communication in Development and Cancer · McMillen P, Oudin MJ, Levin M, Payne SL8