ArticleThe Journal of biological chemistry2015
Functional characterization of CaVα2δ mutations associated with sudden cardiac death.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Casein Kinase 2 Regulates the Intrinsic Activity of L-Type Calcium Currents in Cardiomyocytes.International journal of molecular sciences · 2025Article
- Advanced Atrioventricular Block in Athletes: Prevalence and Role of Anti-Ro/Sjögren Syndrome-Related Antigen A Antibodies.Journal of the American Heart Association · 2024Article
- Microevolutionary mechanism of high-altitude adaptation in Tibetan chicken populations from an elevation gradient.Evolutionary applications · 2022Article
- Deciphering the Interactions of SARS-CoV-2 Proteins with Human Ion Channels Using Machine-Learning-Based Methods.Pathogens (Basel, Switzerland) · 2022Article
- Sympathetic Stimulation Upregulates the CaCells · 2022Article
- Role of High Voltage-Gated CaCells · 2021Review
- Commentary: Peptide-Based Targeting of the L-Type Calcium Channel Corrects the Loss-of-Function Phenotype of Two Novel Mutations of theFrontiers in physiology · 2021Article
- Peptide-Based Targeting of the L-Type Calcium Channel Corrects the Loss-of-Function Phenotype of Two Novel Mutations of theFrontiers in physiology · 2020Article
- Region-based interaction detection in genome-wide case-control studies.BMC medical genomics · 2019Article
- An African loss-of-function CACNA1C variant p.T1787M associated with a risk of ventricular fibrillation.Scientific reports · 2018Article
- Calcium channel gating.Pflugers Archiv : European journal of physiology · 2018Review
- αThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- A three-way inter-molecular network accounts for the CaThe Journal of biological chemistry · 2018Article
- Negatively charged residues in the first extracellular loop of the L-type CaThe Journal of biological chemistry · 2017Article
- Proteolytic cleavage of the hydrophobic domain in the CaThe Journal of biological chemistry · 2017Article
- Loss of αDiabetes · 2017Article
- Voltage-gated calcium channels and their auxiliary subunits: physiology and pathophysiology and pharmacology.The Journal of physiology · 2016Review
- Determination of the Relative Cell Surface and Total Expression of Recombinant Ion Channels Using Flow Cytometry.Journal of visualized experiments : JoVE · 2016Article
- The α2δ-1 subunit remodels CaV1.2 voltage sensors and allows Ca2+ influx at physiological membrane potentials.The Journal of general physiology · 2016Article
- Identification of Glycosylation Sites Essential for Surface Expression of the CaVα2δ1 Subunit and Modulation of the Cardiac CaV1.2 Channel Activity.The Journal of biological chemistry · 2016Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
L-type Ca(2+) channels play a critical role in cardiac rhythmicity. These ion channels are oligomeric complexes formed by the pore-forming CaVα1 with the auxiliary CaVβ and CaVα2δ subunits. CaVα2δ increases the peak current density and improves the voltage-dependent activation gating of CaV1.2 channels without increasing the surface expression of the CaVα1 subunit. The functional impact of genetic variants of CACNA2D1 (the gene encoding for CaVα2δ), associated with shorter repolarization QT intervals (the time interval between the Q and the T waves on the cardiac electrocardiogram), was investigated after recombinant expression of the full complement of L-type CaV1.2 subunits in human embryonic kidney 293 cells. By performing side-by-side high resolution flow cytometry assays and whole-cell patch clamp recordings, we revealed that the surface density of the CaVα2δ wild-type protein correlates with the peak current density. Furthermore, the cell surface density of CaVα2δ mutants S755T, Q917H, and S956T was not significantly different from the cell surface density of the CaVα2δ wild-type protein expressed under the same conditions. In contrast, the cell surface expression of CaVα2δ D550Y, CaVα2δ S709N, and the double mutant D550Y/Q917H was reduced, respectively, by ≈30-33% for the single mutants and by 60% for the latter. The cell surface density of D550Y/Q917H was more significantly impaired than protein stability, suggesting that surface trafficking of CaVα2δ was disrupted by the double mutation. Co-expression with D550Y/Q917H significantly decreased CaV1.2 currents as compared with results obtained with CaVα2δ wild type. It is concluded that D550Y/Q917H reduced inward Ca(2+) currents through a defect in the cell surface trafficking of CaVα2δ. Altogether, our results provide novel insight in the molecular mechanism underlying the modulation of CaV1.2 currents by CaVα2δ.
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