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Last update 23 Jan 2025

CACNA2D1

Last update 23 Jan 2025

Basic Info

Synonyms

CACNA2, CACNA2D1, CACNL2A

+ [11]

Introduction

The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel (PubMed:35293990). Plays an important role in excitation-contraction coupling (By similarity).

Drugs associated with CACNA2D1

Crisugabalin

Target

CACNA2D1

Mechanism

CACNA2D1 blockers

Active Org.

Haisco Pharmaceutical Group Co., Ltd.

Originator Org.

Haisco Pharmaceutical Group Co., Ltd.

Active Indication

Neuralgia, Postherpetic [+7]

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date15 May 2024

Mirogabalin Besilate

Target

CACNA2D1 x CACNA2D2

Mechanism

CACNA2D1 blockers [+1]

Active Org.

Daiichi Sankyo Co., Ltd. [+1]

Originator Org.

Daiichi Sankyo Co., Ltd.

Active Indication

Diabetic peripheral neuropathic pain [+1]

Inactive Indication

Chronic Kidney Diseases [+2]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date08 Jan 2019

Gabapentin Enacarbil

Target

CACNA2D1 x CACNA2D2

Mechanism

CACNA2D1 blockers [+1]

Active Org.

Azurity Pharmaceuticals, Inc. [+1]

Originator Org.

XenoPort, Inc.

Active Indication

Neuralgia, Postherpetic [+1]

Inactive Indication

Alcohol Use Disorder [+2]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date06 Apr 2011

1,769

Clinical Trials associated with CACNA2D1

NCT06614322

/ Not yet recruitingPhase 2IIT

Sensory Phenotyping to Enhance Neuropathic Pain Drug Development (SPENDD): a Randomized, Double-blinded Cross-over Clinical Trial Aimed At Investigating Whether Bedside Quantitative Sensory Testing Can Predict Response to Analgesics.

The goal of this clinical trial is to determine whether quantitative sensory testing (QST) can be used to classify participants into pain sub-groups and predict who will respond best to certain pain treatments in participants with painful peripheral neuropathy.
The analgesic effect is evaluated by measuring pain intensity and Patient Global Impression of Change (PGIC).
This study is a 3-period cross-over trial. This means researchers will compare 3 different drugs (pregabalin, duloxetine, and placebo) over a period of 19 weeks.
Participants will:
* Undergo a quantitative sensory testing (QST) exam.
* Provide a blood sample.
* Complete questionnaires on the computer.
* Take the study drug as instructed.

Start Date01 Sep 2025

Sponsor / Collaborator

University of Rochester

[+1]

ACTRN12624001359527

/ Not yet recruitingPhase 3IIT

A Phase III double-blind placebo-controlled randomised controlled trial to evaluate effectiveness of early treatment with pregabalin in the development of chronic pain in adults with acute whiplash injury

Start Date24 Feb 2025

Sponsor / Collaborator

The University of Queensland

NCT06781489

/ RecruitingPhase 4IIT

Pain Reduction Caused by the Combined Treatment of Neural Mobilization, Oral Gabapentin and Oral Ibuprofen Arginine in the Treatment of Carpal Tunnel Syndrome

In the present investigation the pain reduction effects of a physiotherapy technique combined with gabapentin and ibuprofen arginine will be compared to those produced by an ibuprofen arginine (only) treatment, in subjects who suffer the signs and symptoms of carpal tunnel syndrome.

Start Date01 Feb 2025

Sponsor / Collaborator

Universidad Europea de Madrid SAU

100 Clinical Results associated with CACNA2D1

100 Translational Medicine associated with CACNA2D1

0 Patents (Medical) associated with CACNA2D1

184

Literatures (Medical) associated with CACNA2D1

01 Feb 2025·Poultry Science

Exploring variances in meat quality between Qingyuan partridge chicken and Cobb broiler: Insights from combined multi-omics analysis

Article

Author: Li, Zhenhui ; Cai, Bolin ; Wu, Ruiquan ; Zhang, Zhaofeng ; Cai, Danfeng ; Kong, Shaofen ; Mo, Yu ; Yang, Xin ; Zhou, Zhen ; Nie, Qinghua ; Zhang, Ruitong

Previously, animal breeding prioritized enhancing key economic traits to improve production efficiency, leading to a gradual difference in meat quality. However, the genetic factors influencing meat quality remain unclear. To identify key genetic pathways contributing to meat quality, native Chinese yellow-feathered chicken (Qingyuan Partridge Chicken, QPC; female, n=10), and commercial chicken broiler (Cobb broiler, CB; female, n=10) were used for meat quality assessment through metabolomics, proteomics, and phosphoproteomics sequencing. The results show that QPC had lower pH (93.12%), shear force (81.46%), cooking loss (69.29%), moisture content (93.24%) and muscle fiber area (46.04%), but higher meat color values (a*(163.65%) and b*(250.27%)), drip loss (146.32%), and intramuscular fat content (382.01%) than CB (p < 0.05). Metabolomic, proteomic, and phosphoproteomic analyses were jointly conducted, revealing significant differences in energy metabolism strategies. Higher glycolytic enzyme activity was observed in QPC (ENO1, GAPDH, GPI, PFKM, PKM, and TPI1, p < 0.05), while more energetic phosphate compounds were stored in CB. CB had higher Na⁺/K⁺ Pump protein abundance (SCN4A, LOC107051305, ATP1B4, ATP12A, ATP1A1, and ATP1A2, p < 0.05) and phosphorylation (ATP1A2-Ser662, p < 0.05) and Ca²⁺ channel protein abundance (ATP2B4, SRL, CACNB1, CACNA1S, CACNA2D1, CAMK2G, LOC107050717 and TNNC2, p < 0.05) than QPC. In QPC, CAMKII autophosphorylation activated downstream protein and increased Ca²⁺. These results suggest CB is more contractile than QPC, contributing to meat quality between CB and QPC.

01 Jan 2025·Journal of Neurochemistry

A biallelic mutation in CACNA2D2 associated with developmental and epileptic encephalopathy affects calcium channel‐dependent as well as synaptic functions of α₂δ‐2

Article

Author: Tuluc, Petronel ; Ablinger, Cornelia ; Haddad, Sabrin ; Ortner, Nadine J. ; Campiglio, Marta ; Hessenberger, Manuel ; Obermair, Gerald J. ; Stanika, Ruslan

Abstractα2δ proteins serve as auxiliary subunits of voltage‐gated calcium channels and regulate channel membrane expression and current properties. Besides their channel function, α2δ proteins regulate synapse formation, differentiation, and synaptic wiring. Considering these important functions, it is not surprising that CACNA2D1‐4, the genes encoding for α2δ‐1 to ‐4 isoforms, have been implicated in neurological, neurodevelopmental, and neuropsychiatric disorders. Mutations in CACNA2D2 have been associated with developmental and epileptic encephalopathy (DEE) and cerebellar atrophy. In our present study, we performed a detailed functional characterization of the p.R593P mutation in α2δ‐2, a homozygous mutation previously identified in two siblings with DEE. Importantly, we analyzed both calcium channel‐dependent as well as synaptic functions of α2δ‐2. Our data show that the corresponding p.R596P mutation in mouse α2δ‐2 drastically decreases membrane expression and synaptic targeting of α2δ‐2. This defect correlates with altered biophysical properties of postsynaptic CaV1.3 channel but has no effect on presynaptic CaV2.1 channels upon heterologous expression in tsA201 cells. However, homologous expression of α2δ‐2_R596P in primary cultures of hippocampal neurons affects the ability of α2δ‐2 to induce a statistically significant increase in the presynaptic abundance of endogenous CaV2.1 channels and presynaptic calcium transients. Moreover, our data demonstrate that in addition to lowering membrane expression, the p.R596P mutation reduces the trans‐synaptic recruitment of GABAA receptors and presynaptic synapsin clustering in glutamatergic synapses. Lastly, the α2δ‐2_R596P reduces the amplitudes of glutamatergic miniature postsynaptic currents in transduced hippocampal neurons. Taken together, our data strongly link the human biallelic p.R593P mutation to the underlying severe neurodevelopmental disorder and highlight the importance of studying α2δ mutations not only in the context of channelopathies but also synaptopathies.

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01 Dec 2024·Journal of Cachexia, Sarcopenia and Muscle

Molecular determinants of skeletal muscle force loss in response to 5 days of dry immersion in human

Article

Author: Bastide, Bruno ; Montel, Valérie ; Castells, Josiane ; Allibert, Valentine ; Chopard, Angèle ; Durieux, Anne‐Cécile ; Treffel, Loïc ; Stevens, Laurence ; Freyssenet, Damien ; Brioche, Thomas ; Cochon, Laetitia ; Velarde, Mathias ; Morel, Jérome ; Sempore, Michel‐Yves

AbstractBackgroundAstronauts in Earth's orbit experience microgravity, resulting in a decline of skeletal muscle mass and function. On Earth, models simulating microgravity have shown that the extent of the loss in muscle force is greater than the loss in muscle mass. The reasons behind this disproportionate loss of muscle force are still poorly understood. In the present study, we hypothesize that alongside the loss in skeletal muscle mass, modifications in the expression profile of genes encoding critical determinants of resting membrane potential, excitation‐contraction coupling and Ca2+ handling contribute to the decline in skeletal muscle force.MethodsHealthy male volunteers (n = 18) participated in a 5‐day dry immersion (DI) study, an Earth‐based model of simulated microgravity. Muscle force measurement and MRI analysis of the cross‐sectional area of thigh muscles were performed before and after DI. Biopsies of the vastus lateralis skeletal muscle performed before and after DI were used for the determination Ca2+ properties of isolated muscle fibres, molecular and biochemical analyses.ResultsThe extent of the decline in force, measured as maximal voluntary contraction of knee extensors (−11.1%, P < 0.01) was higher than the decline in muscle mass (−2.5%, P < 0.01). The decline in muscle mass was molecularly supported by a significant repression of the anabolic IGF‐1/Akt/mTOR pathway (−19.9% and −40.9% in 4E‐BP1 and RPS6 phosphorylation, respectively), a transcriptional downregulation of the autophagy‐lysosome pathway and a downregulation in the mRNA levels of myofibrillar protein slow isoforms. At the single fibre level, biochemical and tension‐pCa curve analyses showed that the loss in force was independent of fibre type (−11% and −12.3% in slow and fast fibres, respectively) and Ca2+ activation properties. Finally, we showed a significant remodelling in the expression of critical players of resting membrane potential (aquaporin 4: −24.9%, ATP1A2: +50.4%), excitation‐contraction coupling (CHRNA1: +75.1%, CACNA2D1: −23.5%, JPH2: −24.2%, TRDN: −15.6%, S100A1: +27.2%), and Ca2+ handling (ATP2A2: −32.5%, CASQ1: −15%, ORAI1: −36.2%, ATP2B1: −19.1%).ConclusionsThese findings provide evidence that a deregulation in the expression profile of critical molecular determinants of resting membrane potential, excitation‐contraction coupling, and Ca2+ handling could be involved in the loss of muscle force induced by DI. They also provide the paradigm for the understanding of muscle force loss during prolonged bed rest periods as those encountered in intensive care unit.

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CACNA2D1

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