Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
10.0
5.6
Journals
IJMS
Special Issues
Membrane Channels in Intercellular Communication
ijms-logo
Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Membrane Channels in Intercellular Communication

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 31 December 2026 | Viewed by 4088

Editors

Prof. Dr. Camillo Peracchia

E-Mail Website
Guest Editor
School of Medicine and Dentistry 601 Elmwood Ave, University of Rochester Medical Center, Rochester, NY 14642, USA
Interests: Gap junctions; connexins; cell communication; calmodulin; calcium; channel gating
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Jean Jiang

E-Mail Website
Guest Editor
Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229, USA
Interests: gap junctions and hemichannels; connexins; signaling transmission; breast cancer; osteosarcoma; metastasis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Most vertebrate and invertebrate cells exchange ions and small cytosolic molecules directly via cell–cell channels that are clustered at gap junctions. Gap junction-mediated cell–cell communication is an important mechanism that allows cells to maintain homeostasis and coordinate numerous functions. Conversely, blocked cell–cell communication, known as cell–cell uncoupling, is known to cause many diseases. Each gap junction channel is formed by the interaction of two hemichannels, which create a hydrophilic pathway that spans both plasma membranes and the narrow extracellular space (gap). In turn, each hemichannel is an oligomer of six proteins, known as connexins in vertebrates and innexins in invertebrates. Gap junction channels are regulated by gating mechanisms that are sensitive to changes in cytosolic calcium (Ca2+i), pHi, and membrane potential and trans junctional voltage (Vj) gradients. In the mid-1980s, the cloning of connexin/innexin cDNAs paved the way for the study of gap junction channelopathies. To date, at least thirty-five genetic diseases caused by mutations of eleven different connexins genes have been identified; they are known to result in numerous structural and functional defects in the central and peripheral nervous system, as well as in the heart, skin, eyes, teeth, ears, bone, hair, nails, and lymphatic system. While all these diseases are caused by connexin mutations, minimal attention has been given to potential diseases caused by mutations of connexin-associated molecules. An important accessory of gap junctions is the protein calmodulin (CaM), a highly sensitive modulator of Ca2+i known to play a key role in channel gating and gap junction formation. Other important accessory proteins are enzymes like kinases and phosphatases which, respectively, phosphorylate and dephosphorylate connexins, altering channel permeability and affecting connexin assembly into hemichannels.

This issue aims to publish review articles and/or original papers that highlight important findings on the functions of direct cell–cell communication and the pathological consequences of connexin mutations. It will also explore hypotheses, speculations, suggestions, and ideas that can be tested experimentally.

Prof. Dr. Camillo Peracchia
Prof. Dr. Jean Jiang
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gap junctions
  • connexins
  • innexins
  • channels
  • hemichannels
  • connexin mutations
  • channel gating
  • chemical gating
  • voltage gating
  • cell–cell coupling
  • cell-cell uncoupling
  • cell communication
  • intercellular communication
  • calcium
  • pH

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

32 pages, 6139 KB  
Article
CLARISA: Connexin-43 Lateralization Automated ROI-Based Image Signal Analyzer
by Daniel Gattari, Joseba Sancho-Zamora, Debora Chan, Natalia Jorgelina Prado, Emiliano Raúl Diez, Mariano Llamedo Soria and Mario Rossi
Int. J. Mol. Sci. 2026, 27(11), 5033; https://doi.org/10.3390/ijms27115033 - 2 Jun 2026
Viewed by 524
Abstract
Connexin-43 (CX43) lateralization in ventricular myocardium has been associated with abnormal impulse propagation and increased arrhythmia susceptibility. Its quantitative assessment in histological sections remains challenging because previous methods require segmentation of individual cardiomyocytes and rely on geometric rules applied to segmented cell profiles. [...] Read more.
Connexin-43 (CX43) lateralization in ventricular myocardium has been associated with abnormal impulse propagation and increased arrhythmia susceptibility. Its quantitative assessment in histological sections remains challenging because previous methods require segmentation of individual cardiomyocytes and rely on geometric rules applied to segmented cell profiles. Here, we present CLARISA, a segmentation-free, ROI-based deep learning framework that classifies CX43-positive regions as terminal or lateralized directly from fluorescence images. An expert-annotated dataset was generated from left-ventricular cryosections of Wistar rat hearts, in which CX43-positive regions were labeled according to their distribution pattern. A dual-stream EfficientNetV2-S classifier was trained to capture both local and contextual ROI morphology. We also developed a semi-automated whole-section inference module to generate spatial lateralization probability maps and global percent lateralization estimates. On the held-out test set, CLARISA achieved a ROC-AUC of 0.904 (95% bootstrap CI: 0.828–0.960) and a PR-AUC of 0.808 (95% bootstrap CI: 0.682–0.913), supporting the feasibility of automated ROI classification for CX43 lateralization assessment. When deployed on whole tissue sections, including an independently analyzed section not used during model development, CLARISA generated spatial maps that captured heterogeneous CX43 organization and produced a global percent lateralization estimate closely aligned with expert annotation, differing by only 1.30 percentage points over the same detected CX43-positive area. Comparison with a previously published segmentation-based method further indicated that ROI-based and cell-segmentation-based approaches provide related but non-equivalent readouts of CX43 lateralization. The ROI-based design additionally reduces annotation burden—requiring classification of discrete CX43-positive signal rather than complex cardiomyocyte delineation—and ensures that all detected CX43-positive signal contributes to the lateralization estimate regardless of cell boundaries. These results establish CLARISA as a proof-of-principle framework for scalable, segmentation-free CX43 lateralization assessment in cardiac tissue. Further validation across larger, independent, and more heterogeneous datasets will be required to assess robustness, portability across imaging conditions, and translational applicability. The complete codebase, pretrained model, image data, and expert annotation tool are publicly available. Full article
(This article belongs to the Special Issue Membrane Channels in Intercellular Communication)
►▼ Show Figures

Figure 1

Review

Jump to: Research

23 pages, 9703 KB  
Review
Connexin 26 in Hearing Health and Disease: StructuralFoundations, Mutation Mechanisms, and Therapeutic Perspectives
by Weihua Qiu, Kaelah Schneider and Youzhong Guo
Int. J. Mol. Sci. 2026, 27(11), 4831; https://doi.org/10.3390/ijms27114831 - 27 May 2026
Viewed by 1645
Abstract
Mutations in gap junction protein β-2 (GJB2), encoding Connexin 26 (Cx26), are the most common genetic cause of hearing loss, responsible for up to 50% of inherited non-syndromic cases worldwide. This review covers Cx26 from three perspectives: protein structure, mutant disease mechanisms, and [...] Read more.
Mutations in gap junction protein β-2 (GJB2), encoding Connexin 26 (Cx26), are the most common genetic cause of hearing loss, responsible for up to 50% of inherited non-syndromic cases worldwide. This review covers Cx26 from three perspectives: protein structure, mutant disease mechanisms, and treatment approaches. Structurally, 12 Cx26 subunits assemble into a gap junction channel connecting neighboring cells, enabling exchange of ions and signaling molecules; activity is regulated by calcium, pH, and CO2. In the cochlea, Cx26 channels are required for the development of sound-sensing hair cells, maintenance of the electrical gradient needed for hearing, and energy supply during sound processing. GJB2 mutations cause hearing loss through three mechanisms, complete loss of functional protein, failure of channel assembly or membrane delivery, and abnormal channel gating, that damage cochlear cells. Severity ranges from profound congenital deafness to gradual decline, depending on which mutations are inherited. Gene therapy, genome editing, and pharmacological approaches are under investigation; cochlear implantation remains the current standard of care. Full article
(This article belongs to the Special Issue Membrane Channels in Intercellular Communication)
►▼ Show Figures

Figure 1

27 pages, 13894 KB  
Review
History of Gap Junction Architecture and Potential Role of Calmodulin in Channel Arrays
by Camillo Peracchia
Int. J. Mol. Sci. 2025, 26(23), 11337; https://doi.org/10.3390/ijms262311337 - 24 Nov 2025
Cited by 3 | Viewed by 1064
Abstract
This review article focuses first on the historical development of present understanding of gap junction channel architecture, one of its goals being to enlighten younger generations of scientists about the early steps of this field that begun over half a century ago. Early [...] Read more.
This review article focuses first on the historical development of present understanding of gap junction channel architecture, one of its goals being to enlighten younger generations of scientists about the early steps of this field that begun over half a century ago. Early findings on gap junction architecture are reviewed as follows. The channels cross the membrane and project from the membrane surfaces; they are made of six subunits (hexamers) and show dimples on both ends, which represent inner and outer openings of the channel. Images of the central dimples on both channel ends (channel pores) seen in freeze-fracture replicas correspond to the electron-opaque spots visible in negatively stained sections and in isolated junctions. The channels are linked to each other extracellularly. Calmodulin (CaM) is a major accessory protein of gap junctions that is involved in channel gating and gap junction formation and is also likely to play a key role in determining different patterns of channel aggregation. Full article
(This article belongs to the Special Issue Membrane Channels in Intercellular Communication)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop