ArticleScientific reports2012
Calcineurin Controls Voltage-Dependent-Inactivation (VDI) of the Normal and Timothy Cardiac Channels.
Article in Scientific reports, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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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.
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Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- Unexpected impairment ofNature cardiovascular research · 2023Article
- Upregulation of N-Type Voltage-Gated Calcium Channels Induces Neuropathic Pain in Experimental Autoimmune Neuritis.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Update on the Molecular Genetics of Timothy Syndrome.Frontiers in pediatrics · 2021Review
- Involvement of Calcium-Dependent Pathway and β Subunit-Interaction in Neuronal Migration and Callosal Projection Deficits Caused by the Cav1.2 I1166T Mutation in Developing Mouse Neocortex.Frontiers in neuroscience · 2021Article
- Calcineurin Antagonizes AMPK to Regulate Lipolysis in Caenorhabditis elegans.Molecules (Basel, Switzerland) · 2017Article
- Arrhythmogenesis in Timothy Syndrome is associated with defects in Ca(2+)-dependent inactivation.Nature communications · 2016Article
- Modeling neurodevelopmental disorders using human pluripotent stem cells.Stem cell reviews and reports · 2014Review
- Exome sequencing helped the fine diagnosis of two siblings afflicted with atypical Timothy syndrome (TS2).BMC medical genetics · 2014Article
- Article
- Modeling Timothy syndrome with iPS cells.Journal of cardiovascular translational research · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ca(2+)-entry in the heart is tightly controlled by Cav1.2 inactivation, which involves Ca(2+)-dependent inactivation (CDI) and voltage-dependent inactivation (VDI) components. Timothy syndrome, a subtype-form of congenital long-QT syndrome, results from a nearly complete elimination of VDI by the G406R mutation in the α(1)1.2 subunit of Cav1.2. Here, we show that a single (A1929P) or a double mutation (H1926A-H1927A) within the CaN-binding site at the human C-terminal tail of α(1)1.2, accelerate the inactivation rate and enhances VDI of both wt and Timothy channels. These results identify the CaN-binding site as the long-sought VDI-regulatory motif of the cardiac channel. The substantial increase in VDI and the accelerated inactivation caused by the selective inhibitors of CaN, cyclosporine A and FK-506, which act at the same CaN-binding site, further support this conclusion. A reversal of enhanced-sympathetic tone by VDI-enhancing CaN inhibitors could be beneficial for improving Timothy syndrome complications such as long-QT and autism.
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Registered trials
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