ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
The ducky(2J) mutation in Cacna2d2 results in reduced spontaneous Purkinje cell activity and altered gene expression.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42 citing papers in PubMed, 71 citations in OpenAlex.
- Biochemistry and physiology of voltage-gated calcium channel trafficking: a target for gabapentinoid drugs.Open biology · 2025Review
- A biallelic mutation in CACNA2D2 associated with developmental and epileptic encephalopathy affects calcium channel-dependent as well as synaptic functions of αJournal of neurochemistry · 2025Article
- Voltage-gated calcium channels in genetic epilepsies.Journal of neurochemistry · 2024Review
- Classification of Current Experimental Models of Epilepsy.Brain sciences · 2024Review
- Modulation of L-type calcium channels in Alzheimer's disease: A potential therapeutic target.Computational and structural biotechnology journal · 2023Review
- Pathophysiological Roles of Auxiliary Calcium Channel αHandbook of experimental pharmacology · 2023Article
- Depleted Calcium Stores and Increased Calcium Entry in Rod Photoreceptors of theInternational journal of molecular sciences · 2022Article
- α2δ-2 is required for depolarization-induced suppression of excitation in Purkinje cells.The Journal of physiology · 2022Article
- Phenotypic Characterization and Brain Structure Analysis of Calcium Channel Subunit αFrontiers in synaptic neuroscience · 2021Article
- Different functions of two putative Drosophila αScientific reports · 2020Article
- α2δ-2 Protein Controls Structure and Function at the Cerebellar Climbing Fiber Synapse.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Increased glutamate transporter-associated anion currents cause glial apoptosis in episodic ataxia 6.Brain communications · 2020Article
- Genetic Associations between Voltage-Gated Calcium Channels and Psychiatric Disorders.International journal of molecular sciences · 2019Review
- Injury-induced maladaptation and dysregulation of calcium channel αBritish journal of pharmacology · 2018Review
- Voltage-gated calcium channel αF1000Research · 2018Review
- Purkinje Cell Signaling Deficits in Animal Models of Ataxia.Frontiers in synaptic neuroscience · 2018Review
- α2δ2 Controls the Function and Trans-Synaptic Coupling of Cav1.3 Channels in Mouse Inner Hair Cells and Is Essential for Normal Hearing.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Voltage-gated calcium channels and their auxiliary subunits: physiology and pathophysiology and pharmacology.The Journal of physiology · 2016Review
- Does modulation of the endocannabinoid system have potential therapeutic utility in cerebellar ataxia?The Journal of physiology · 2016Review
- The Role of Calcium Channels in Epilepsy.Cold Spring Harbor perspectives in medicine · 2016Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The mouse mutant ducky and its allele ducky(2J) represent a model for absence epilepsy characterized by spike-wave seizures and cerebellar ataxia. These mice have mutations in Cacna2d2, which encodes the alpha2delta-2 calcium channel subunit. Of relevance to the ataxic phenotype, alpha2delta-2 mRNA is strongly expressed in cerebellar Purkinje cells (PCs). The Cacna2d2(du2J) mutation results in a 2 bp deletion in the coding region and a complete loss of alpha2delta-2 protein. Here we show that du(2J)/du(2J) mice have a 30% reduction in somatic calcium current and a marked fall in the spontaneous PC firing rate at 22 degrees C, accompanied by a decrease in firing regularity, which is not affected by blocking synaptic input to PCs. At 34 degrees C, du(2J)/du(2J) PCs show no spontaneous intrinsic activity. Du(2J)/du(2J) mice also have alterations in the cerebellar expression of several genes related to PC function. At postnatal day 21, there is an elevation of tyrosine hydroxylase mRNA and a reduction in tenascin-C gene expression. Although du(2J)/+ mice have a marked reduction in alpha2delta-2 protein, they show no fall in PC somatic calcium currents or increase in cerebellar tyrosine hydroxylase gene expression. However, du(2J)/+ PCs do exhibit a significant reduction in firing rate, correlating with the reduction in alpha2delta-2. A hypothesis for future study is that effects on gene expression occur as a result of a reduction in somatic calcium currents, whereas effects on PC firing occur as a long-term result of loss of alpha2delta-2 and/or a reduction in calcium currents and calcium-dependent processes in regions other than the soma.
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