ArticleNature communications2016
Arrhythmogenesis in Timothy Syndrome is associated with defects in Ca(2+)-dependent inactivation.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Geno- and phenotypic characteristics and clinical outcomes ofFrontiers in cardiovascular medicine · 2022Pooled it
- Timothy syndrome and CACNA1C-Related Disorder: first international language and management guidelines consensus statement.European journal of human genetics : EJHG · 2026Review
- Calmodulinopathy variants impair CaV1.3 and CaV2.1 regulation.The Journal of general physiology · 2026Article
- Functional consequences of calmodulin variants identified among schizophrenia patients and controls.Translational psychiatry · 2025Article
- Timothy Syndrome and CACNA1C-Related Disorder: First International Language and Management Guidelines Consensus Statement.Research square · 2025Article
- Disruptions in primary visual cortex physiology and function in a mouse model of Timothy syndrome.Cerebral cortex (New York, N.Y. : 1991) · 2025Article
- CommonGenome research · 2025Article
- Inactivation of CaV1 and CaV2 channels.The Journal of general physiology · 2025Review
- Synaptic plasticity deficits in a mouse model of Timothy syndrome: LTP saturation and its pharmacological rescue by nifedipine.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Arrhythmogenic calmodulin variants D131E and Q135P disrupt interaction with the L-type voltage-gated CaActa physiologica (Oxford, England) · 2025Article
- SomaticHypertension (Dallas, Tex. : 1979) · 2024Article
- A Natural History Study of Timothy Syndrome.Orphanet journal of rare diseases · 2024Article
- Synaptic homeostasis transiently leverages Hebbian mechanisms for a multiphasic response to inactivity.Cell reports · 2024Article
- Asymmetric contribution of a selectivity filter gate in triggering inactivation of CaV1.3 channels.The Journal of general physiology · 2024Article
- Transmural APD heterogeneity determines ventricular arrhythmogenesis in LQT8 syndrome: Insights from Bidomain computational modeling.PloS one · 2024Article
- Knock-in swine model reveals new arrhythmia mechanism in Timothy syndrome.Nature cardiovascular research · 2024Article
- Maresin1 ameliorates MSU crystal-induced inflammation by upregulating Prdx5 expression.Molecular medicine (Cambridge, Mass.) · 2023Article
- Article
- Current updates on arrhythmia within Timothy syndrome: genetics, mechanisms and therapeutics.Expert reviews in molecular medicine · 2023Review
- Regulation of Cardiac Cav1.2 Channels by Calmodulin.International journal of molecular sciences · 2023Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Timothy Syndrome (TS) is a multisystem disorder, prominently featuring cardiac action potential prolongation with paroxysms of life-threatening arrhythmias. The underlying defect is a single de novo missense mutation in CaV1.2 channels, either G406R or G402S. Notably, these mutations are often viewed as equivalent, as they produce comparable defects in voltage-dependent inactivation and cause similar manifestations in patients. Yet, their effects on calcium-dependent inactivation (CDI) have remained uncertain. Here, we find a significant defect in CDI in TS channels, and uncover a remarkable divergence in the underlying mechanism for G406R versus G402S variants. Moreover, expression of these TS channels in cultured adult guinea pig myocytes, combined with a quantitative ventricular myocyte model, reveals a threshold behaviour in the induction of arrhythmias due to TS channel expression, suggesting an important therapeutic principle: a small shift in the complement of mutant versus wild-type channels may confer significant clinical improvement.
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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.