ArticleThe Journal of physiology2019
Impaired chromaffin cell excitability and exocytosis in autistic Timothy syndrome TS2-neo mouse rescued by L-type calcium channel blockers.
Article in The Journal of physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Calcium channelopathies and intellectual disability: a systematic review.Orphanet journal of rare diseases · 2021Pooled it
- Mitochondrial and lysosomal dysfunctions might be involved in the pathogenesis of the CACNA1A-related neurodevelopmental disorders according to in vitro studies.Biological research · 2025Article
- Beyond the brain: early autonomic dysfunction in Alzheimer's disease.Acta neuropathologica communications · 2025Article
- Disruptions in primary visual cortex physiology and function in a mouse model of Timothy syndrome.Cerebral cortex (New York, N.Y. : 1991) · 2025Article
- Synaptic plasticity deficits in a mouse model of Timothy syndrome: LTP saturation and its pharmacological rescue by nifedipine.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Multiple beta cell-independent mechanisms drive hypoglycemia in Timothy syndrome.Nature communications · 2024Article
- Asymmetric contribution of a selectivity filter gate in triggering inactivation of CaV1.3 channels.The Journal of general physiology · 2024Article
- The human channel gating-modifying A749G CACNA1D (Cav1.3) variant induces a neurodevelopmental syndrome-like phenotype in mice.JCI insight · 2023Article
- Forty years of the adrenal chromaffin cell through ISCCB meetings around the world.Pflugers Archiv : European journal of physiology · 2023Review
- Current updates on arrhythmia within Timothy syndrome: genetics, mechanisms and therapeutics.Expert reviews in molecular medicine · 2023Review
- Two firing modes and well-resolved NaPflugers Archiv : European journal of physiology · 2023Article
- Disruption of mitochondrial and lysosomal functions by humanFrontiers in molecular neuroscience · 2023Article
- CACNA1C-Related Channelopathies.Handbook of experimental pharmacology · 2023Review
- Increased CaScientific reports · 2022Article
- CaV1.2 channelopathic mutations evoke diverse pathophysiological mechanisms.The Journal of general physiology · 2022Article
- Article
- Alterations of the Sympathoadrenal Axis Related to the Development of Alzheimer's Disease in the 3xTg Mouse Model.Biology · 2022Article
- DisruptedProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Novel CACNA1C R511Q mutation, located in domain Ⅰ-Ⅱ linker, causes non-syndromic type-8 long QT syndrome.PloS one · 2022Article
- Role of High Voltage-Gated CaCells · 2021Review
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
key pointsTymothy syndrome (TS) is a multisystem disorder featuring cardiac arrhythmias, autism and adrenal gland dysfunction that originates from a de novo point mutation in the gene encoding the Cav1.2 (CACNA1C) L-type channel. To study the role of Cav1.2 channel signals in autism, the autistic TS2-neo mouse has been generated bearing the G406R point-mutation associated with TS type-2. Using heterozygous TS2-neo mice, we report that the G406R mutation reduces the rate of inactivation and shifts leftward the activation and inactivation of L-type channels, causing marked increase of resting Ca ABSTRACT: L-type voltage-gated calcium (Cav1) channels have a key role in long-term synaptic plasticity, sensory transduction, muscle contraction and hormone release. A point mutation in the gene encoding Cav1.2 (CACNA1C) causes Tymothy syndrome (TS), a multisystem disorder featuring cardiac arrhythmias, autism spectrum disorder (ASD) and adrenal gland dysfunction. In the more severe type-2 form (TS2), the missense mutation G406R is on exon 8 coding for the IS6-helix of the Cav1.2 channel. The mutation causes reduced inactivation and induces autism. How this occurs and how Cav1.2 gating-changes alter cell excitability, neuronal firing and hormone release on a molecular basis is still largely unknown. Here, using the TS2-neo mouse model of TS we show that the G406R mutation altered excitability and reduced secretory activity in adrenal chromaffin cells (CCs). Specifically, the TS2 mutation reduced the rate of voltage-dependent inactivation and shifted leftward the activation and steady-state inactivation of L-type channels. This markedly increased the resting 'window' Ca
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