ArticleProceedings of the National Academy of Sciences of the United States of America2005
A CACNA1F mutation identified in an X-linked retinal disorder shifts the voltage dependence of Cav1.4 channel activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.
- Genetic associations between voltage-gated calcium channels and autism spectrum disorder: a systematic review.Molecular brain · 2020Pooled it
- L-type voltage-gated CaEMBO reports · 2026Article
- Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944.The Journal of general physiology · 2026Article
- Expanding the Genotypic Landscape of Congenital Stationary Night Blindness in an Ethnically Diverse Canadian Population.Human mutation · 2026Article
- Quantitative Proteomics Identifies Potential Molecular Adaptations in Mouse Models of Congenital Stationary Night Blindness Type 2.Molecular & cellular proteomics : MCP · 2025Article
- Exploring the potential for gene therapy in Cav1.4-related retinal channelopathies.Channels (Austin, Tex.) · 2025Review
- Inactivation of CaV1 and CaV2 channels.The Journal of general physiology · 2025Review
- Voltage-gated calcium channels in genetic epilepsies.Journal of neurochemistry · 2024Review
- The endoplasmic reticulum membrane protein complex subunitGenes & diseases · 2024Article
- Characterization of two pathological gating-charge substitutions in Cav1.4 L-type calcium channels.Channels (Austin, Tex.) · 2023Article
- Ribbon Synapses and Retinal Disease: Review.International journal of molecular sciences · 2023Review
- Functional Characterization of Four Known Cav2.1 Variants Associated with Neurodevelopmental Disorders.Membranes · 2023Article
- Calcium Channels in Retinal Function and Disease.Annual review of vision science · 2022Review
- The role of voltage-gated ion channels in visual function and disease in mammalian photoreceptors.Pflugers Archiv : European journal of physiology · 2021Review
- Cav1.4 dysfunction and congenital stationary night blindness type 2.Pflugers Archiv : European journal of physiology · 2021Review
- Function of cone and cone-related pathways in CaScientific reports · 2021Article
- Voltage-Gated CaFrontiers in synaptic neuroscience · 2021Review
- Dendritic Integration Dysfunction in Neurodevelopmental Disorders.Developmental neuroscience · 2021Review
- A Review of Genetic and Physiological Disease Mechanisms Associated With Cav1 Channels: Implications for Incomplete Congenital Stationary Night Blindness Treatment.Frontiers in genetics · 2021Article
- Functional impact of a congenital stationary night blindness type 2 mutation depends on subunit composition of CaThe Journal of biological chemistry · 2020Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Light stimuli produce graded hyperpolarizations of the photoreceptor plasma membrane and an associated decrease in a voltagegated calcium channel conductance that mediates release of glutamate neurotransmitter. The Ca(v)1.4 channel is thought to be involved in this process. The CACNA1F gene encodes the poreforming subunit of the Ca(v)1.4 channel and various mutations in CACNA1F cause X-linked incomplete congenital stationary night blindness (CSNB2). The molecular mechanism of the pathology underlying the CSNB2 phenotype remains to be established. Recent clinical investigations of a New Zealand family found a severe visual disorder that has some clinical similarities to, but is clearly distinct from, CSNB2. Here, we report investigations into the molecular mechanism of the pathology of this condition. Molecular genetic analyses identified a previously undescribed nucleotide substitution in CACNA1F that is predicted to encode an isoleucine to threonine substitution at CACNA1F residue 745. The I745T CACNA1F allele produced a remarkable approximately -30-mV shift in the voltage dependence of Ca(v)1.4 channel activation and significantly slower inactivation kinetics in an expression system. These findings imply that substitution of this wild-type residue in transmembrane segment IIS6 may have decreased the energy required to open the channel. Collectively, these findings suggest that a gain-of-function mechanism involving increased Ca(v)1.4 channel activity is likely to cause the unusual phenotype.
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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.