ArticleProceedings of the National Academy of Sciences of the United States of America2013
Manipulating L-type calcium channels in cardiomyocytes using split-intein protein transsplicing.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- A robust expression system reveals distinct gating mechanisms and calmodulin regulation of NaScience advances · 2025Article
- Palmitoylation of the pore-forming subunit of Ca(v)1.2 controls channel voltage sensitivity and calcium transients in cardiac myocytes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- KCNQ2 and KCNQ5 form heteromeric channels independent of KCNQ3.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Macrophage-Dependent Interleukin-6-Production and Inhibition ofInternational journal of molecular sciences · 2021Article
- Cav1.4 dysfunction and congenital stationary night blindness type 2.Pflugers Archiv : European journal of physiology · 2021Review
- Inteins in Science: Evolution to Application.Microorganisms · 2020Review
- Chemical modification of proteins by insertion of synthetic peptides using tandem protein trans-splicing.Nature communications · 2020Article
- Pathophysiology of Calcium Mediated Ventricular Arrhythmias and Novel Therapeutic Options with Focus on Gene Therapy.International journal of molecular sciences · 2019Review
- Roles and Regulation of Voltage-gated Calcium Channels in Arrhythmias.The Journal of innovations in cardiac rhythm management · 2019Review
- A potent voltage-gated calcium channel inhibitor engineered from a nanobody targeted to auxiliary CaeLife · 2019Article
- Intein-mediated protein trans-splicing expands adeno-associated virus transfer capacity in the retina.Science translational medicine · 2019Article
- Engineering selectivity into RGK GTPase inhibition of voltage-dependent calcium channels.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Relevance of tissue specific subunit expression in channelopathies.Neuropharmacology · 2018Review
- Pediatric Dilated Cardiomyopathy-AssociatedJournal of the American Heart Association · 2018Article
- Article
- Efficient generation of bispecific IgG antibodies by split intein mediated protein trans-splicing system.Scientific reports · 2017Article
- Engineering prokaryotic channels for control of mammalian tissue excitability.Nature communications · 2016Article
- Article
- Localized force application reveals mechanically sensitive domains of Piezo1.Nature communications · 2016Article
- Similar molecular determinants on Rem mediate two distinct modes of inhibition of CaChannels (Austin, Tex.) · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Manipulating expression of large genes (>6 kb) in adult cardiomyocytes is challenging because these cells are only efficiently transduced by viral vectors with a 4-7 kb packaging capacity. This limitation impedes understanding structure-function mechanisms of important proteins in heart. L-type calcium channels (LTCCs) regulate diverse facets of cardiac physiology including excitation-contraction coupling, excitability, and gene expression. Many important questions about how LTCCs mediate such multidimensional signaling are best resolved by manipulating expression of the 6.6 kb pore-forming α1C-subunit in adult cardiomyocytes. Here, we use split-intein-mediated protein transsplicing to reconstitute LTCC α1C-subunit from two distinct halves, overcoming the difficulty of expressing full-length α1C in cardiomyocytes. Split-intein-tagged α1C fragments encoding dihydropyridine-resistant channels were incorporated into adenovirus and reconstituted in cardiomyocytes. Similar to endogenous LTCCs, recombinant channels targeted to dyads, triggered Ca(2+) transients, associated with caveolin-3, and supported β-adrenergic regulation of excitation-contraction coupling. This approach lowers a longstanding technical hurdle to manipulating large proteins in cardiomyocytes.
Indexed as
Identifiers
What OpenQuestion holds
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.