ArticleScientific reports2016
An autism-associated mutation in CaV1.3 channels has opposing effects on voltage- and Ca(2+)-dependent regulation.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Impact of CaInternational journal of molecular sciences · 2026Review
- Calmodulinopathy variants impair CaV1.3 and CaV2.1 regulation.The Journal of general physiology · 2026Article
- Inactivation of CaV1 and CaV2 channels.The Journal of general physiology · 2025Review
- The human channel gating-modifying A749G CACNA1D (Cav1.3) variant induces a neurodevelopmental syndrome-like phenotype in mice.JCI insight · 2023Article
- Regulation of Cardiac Cav1.2 Channels by Calmodulin.International journal of molecular sciences · 2023Review
- Germline de novo variant F747S extends the phenotypic spectrum of CACNA1D Ca2+ channelopathies.Human molecular genetics · 2023Article
- CACNA1D-Related Channelopathies: From Hypertension to Autism.Handbook of experimental pharmacology · 2023Review
- Shank3 related muscular hypotonia is accompanied by increased intracellular calcium concentrations and ion channel dysregulation in striated muscle tissue.Frontiers in cell and developmental biology · 2023Article
- The CaNeuropharmacology · 2022Article
- Tuberous Sclerosis Complex (TSC) Inactivation Increases Neuronal Network Activity by Enhancing CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Voltage-Gated CaFrontiers in synaptic neuroscience · 2021Review
- CaThe Journal of biological chemistry · 2020Article
- De novo CACNA1D CaPflugers Archiv : European journal of physiology · 2020Review
- Long non-coding RNA Neat1 regulates adaptive behavioural response to stress in mice.Translational psychiatry · 2020Article
- Neuronal L-Type Calcium Channel Signaling to the Nucleus Requires a Novel CaMKIIα-Shank3 Interaction.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Biophysical classification of aMolecular autism · 2020Article
- An autism-causing calcium channel variant functions with selective autophagy to alter axon targeting and behavior.PLoS genetics · 2019Article
- Genetic Associations between Voltage-Gated Calcium Channels and Psychiatric Disorders.International journal of molecular sciences · 2019Review
- A Selectivity Filter Gate Controls Voltage-Gated Calcium Channel Calcium-Dependent Inactivation.Neuron · 2019Article
- Single-Channel Resolution of the Interaction between C-Terminal CaBiophysical journal · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
CaV1.3 channels are a major class of L-type Ca(2+) channels which contribute to the rhythmicity of the heart and brain. In the brain, these channels are vital for excitation-transcription coupling, synaptic plasticity, and neuronal firing. Moreover, disruption of CaV1.3 function has been associated with several neurological disorders. Here, we focus on the de novo missense mutation A760G which has been linked to autism spectrum disorder (ASD). To explore the role of this mutation in ASD pathogenesis, we examined the effects of A760G on CaV1.3 channel gating and regulation. Introduction of the mutation severely diminished the Ca(2+)-dependent inactivation (CDI) of CaV1.3 channels, an important feedback system required for Ca(2+) homeostasis. This reduction in CDI was observed in two major channel splice variants, though to different extents. Using an allosteric model of channel gating, we found that the underlying mechanism of CDI reduction is likely due to enhanced channel opening within the Ca(2+)-inactivated mode. Remarkably, the A760G mutation also caused an opposite increase in voltage-dependent inactivation (VDI), resulting in a multifaceted mechanism underlying ASD. When combined, these regulatory deficits appear to increase the intracellular Ca(2+) concentration, thus potentially disrupting neuronal development and synapse formation, ultimately leading to ASD.
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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.