ArticleAmerican journal of physiology. Cell physiology2012
Gating of connexin 43 gap junctions by a cytoplasmic loop calmodulin binding domain.
Article in American journal of physiology. Cell physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 67 citations in OpenAlex.
- Trial
- Multi-ion permeation and dynamic conductance modulation in connexin gap junction channels.bioRxiv : the preprint server for biology · 2026Article
- History of Gap Junction Architecture and Potential Role of Calmodulin in Channel Arrays.International journal of molecular sciences · 2025Review
- Article
- Novel 2D/3D Hybrid Organoid System for High-Throughput Drug Screening in iPSC Cardiomyocytes.Therapeutics · 2025Article
- Calcium Role in Gap Junction Channel Gating: Direct Electrostatic or Calmodulin-Mediated?International journal of molecular sciences · 2024Review
- Gap Junction Channel Regulation: A Tale of Two Gates-Voltage Sensitivity of the Chemical Gate and Chemical Sensitivity of the Fast Voltage Gate.International journal of molecular sciences · 2024Review
- Connexins in epidermal health and diseases: insights into their mutations, implications, and therapeutic solutions.Frontiers in physiology · 2024Review
- Article
- The retinal pigment epithelium displays electrical excitability and lateral signal spreading.BMC biology · 2023Article
- CaInternational journal of molecular sciences · 2023Article
- CaFrontiers in cellular neuroscience · 2023Article
- Anesthetics and Cell-Cell Communication: Potential CaInternational journal of molecular sciences · 2022Review
- Review
- Calmodulin-Connexin Partnership in Gap Junction Channel Regulation-Calmodulin-Cork Gating Model.International journal of molecular sciences · 2021Review
- New Insights on the Role of Connexins and Gap Junctions Channels in Adipose Tissue and Obesity.International journal of molecular sciences · 2021Review
- Regulation of Connexin Gap Junctions and Hemichannels by Calcium and Calcium Binding Protein Calmodulin.International journal of molecular sciences · 2020Review
- Article
- Calmodulin Binding to Connexin 35: Specializations to Function as an Electrical Synapse.International journal of molecular sciences · 2020Article
- Calmodulin-Cork Model of Gap Junction Channel Gating-One Molecule, Two Mechanisms.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Calmodulin (CaM) binding sites were recently identified on the cytoplasmic loop (CL) of at least three α-subfamily connexins (Cx43, Cx44, Cx50), while Cx40 does not have this putative CaM binding domain. The purpose of this study was to examine the functional relevance of the putative Cx43 CaM binding site on the Ca(2+)-dependent regulation of gap junction proteins formed by Cx43 and Cx40. Dual whole cell patch-clamp experiments were performed on stable murine Neuro-2a cells expressing Cx43 or Cx40. Addition of ionomycin to increase external Ca(2+) influx reduced Cx43 gap junction conductance (G(j)) by 95%, while increasing cytosolic Ca(2+) concentration threefold. By contrast, Cx40 G(j) declined by <20%. The Ca(2+)-induced decline in Cx43 G(j) was prevented by pretreatment with calmidazolium or reversed by the addition of 10 mM EGTA to Ca(2+)-free extracellular solution, if Ca(2+) chelation was commenced before complete uncoupling, after which g(j) was only 60% recoverable. The Cx43 CL(136-158) mimetic peptide, but not the scrambled control peptide, or Ca(2+)/CaM-dependent kinase II 290-309 inhibitory peptide also prevented the Ca(2+)/CaM-dependent decline of Cx43 G(j). Cx43 gap junction channel open probability decreased to zero without reductions in the current amplitudes during external Ca(2+)/ionomycin perfusion. We conclude that Cx43 gap junctions are gated closed by a Ca(2+)/CaM-dependent mechanism involving the carboxyl-terminal quarter of the connexin CL domain. This study provides the first evidence of intrinsic differences in the Ca(2+) regulatory properties of Cx43 and Cx40.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.