ArticleBasic research in cardiology2013
Deletion of the last five C-terminal amino acid residues of connexin43 leads to lethal ventricular arrhythmias in mice without affecting coupling via gap junction channels.
Article in Basic research in cardiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 69 citations in OpenAlex.
- Atrial cardiomyopathy resulting from loss of plakophilin-2 expression: Response to adrenergic stimulation and implications for the exercise response.The Journal of physiology · 2025Article
- Macrophages enhance sodium channel expression in cardiomyocytes.Basic research in cardiology · 2024Article
- Connexin43 promotes exocytosis of damaged lysosomes through actin remodelling.The EMBO journal · 2024Article
- Mechanisms of Intracellular Communication in Cancer and Pathogen Spreading.Results and problems in cell differentiation · 2024Review
- The intercalated disc: a unique organelle for electromechanical synchrony in cardiomyocytes.Physiological reviews · 2023Review
- Article
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- Connexin Mutations and Hereditary Diseases.International journal of molecular sciences · 2022Review
- Impaired Cx43 gap junction endocytosis causes morphological and functional defects in zebrafish.Molecular biology of the cell · 2021Article
- Mechanisms of Arrhythmias in the Brugada Syndrome.International journal of molecular sciences · 2020Review
- Inhibition of MicroRNA-206 Ameliorates Ischemia-Reperfusion Arrhythmia in a Mouse Model by Targeting Connexin43.Journal of cardiovascular translational research · 2020Article
- Heritable arrhythmia syndromes associated with abnormal cardiac sodium channel function: ionic and non-ionic mechanisms.Cardiovascular research · 2020Review
- From Genome-Wide Association Studies to Cardiac Electrophysiology: Through the Maze of Biological Complexity.Frontiers in physiology · 2020Review
- Connexin 43 dephosphorylation contributes to arrhythmias and cardiomyocyte apoptosis in ischemia/reperfusion hearts.Basic research in cardiology · 2019Article
- Combination of HGF and IGF-1 promotes connexin 43 expression and improves ventricular arrhythmia after myocardial infarction through activating the MAPK/ERK and MAPK/p38 signaling pathways in a rat model.Cardiovascular diagnosis and therapy · 2019Article
- The carboxy-terminus, a key regulator of protein function.Critical reviews in biochemistry and molecular biology · 2019Review
- Connexins and Disease.Cold Spring Harbor perspectives in biology · 2018Review
- Protein⁻Protein Interactions with Connexin 43: Regulation and Function.International journal of molecular sciences · 2018Review
- Intracellular trafficking pathways of Cx43 gap junction channels.Biochimica et biophysica acta. Biomembranes · 2018Review
- Unmasking the molecular link between arrhythmogenic cardiomyopathy and Brugada syndrome.Nature reviews. Cardiology · 2017Review
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Authors and funding
19 authors at 9 institutions in 3 countries.
Funding
Abstract
The cardiac intercalated disc harbors mechanical and electrical junctions as well as ion channel complexes mediating propagation of electrical impulses. Cardiac connexin43 (Cx43) co-localizes and interacts with several of the proteins located at intercalated discs in the ventricular myocardium. We have generated conditional Cx43D378stop mice lacking the last five C-terminal amino acid residues, representing a binding motif for zonula occludens protein-1 (ZO-1), and investigated the functional consequences of this mutation on cardiac physiology and morphology. Newborn and adult homozygous Cx43D378stop mice displayed markedly impaired and heterogeneous cardiac electrical activation properties and died from severe ventricular arrhythmias. Cx43 and ZO-1 were co-localized at intercalated discs in Cx43D378stop hearts, and the Cx43D378stop gap junction channels showed normal coupling properties. Patch clamp analyses of isolated adult Cx43D378stop cardiomyocytes revealed a significant decrease in sodium and potassium current densities. Furthermore, we also observed a significant loss of Nav1.5 protein from intercalated discs in Cx43D378stop hearts. The phenotypic lethality of the Cx43D378stop mutation was very similar to the one previously reported for adult Cx43 deficient (Cx43KO) mice. Yet, in contrast to Cx43KO mice, the Cx43 gap junction channel was still functional in the Cx43D378stop mutant. We conclude that the lethality of Cx43D378stop mice is independent of the loss of gap junctional intercellular communication, but most likely results from impaired cardiac sodium and potassium currents. The Cx43D378stop mice reveal for the first time that Cx43 dependent arrhythmias can develop by mechanisms other than impairment of gap junction channel function.
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