ArticleThe Journal of physiology2014
Kv3.3 channels harbouring a mutation of spinocerebellar ataxia type 13 alter excitability and induce cell death in cultured cerebellar Purkinje cells.
Article in The Journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
- A novel early onset spinocerebellar ataxia 13 BAC mouse model with cerebellar atrophy, tremor, and ataxic gait.Experimental animals · 2025Article
- Voltage-gated potassium channels as a potential therapeutic target for the treatment of neurological and psychiatric disorders.Frontiers in cellular neuroscience · 2024Review
- Clinical and electrophysiological features of SCN8A variants causing episodic or chronic ataxia.EBioMedicine · 2023Article
- The involvement of Purkinje cells in progressive myoclonic epilepsy: Focus on neuronal ceroid lipofuscinosis.Neurobiology of disease · 2023Review
- Epilepsy as the symptom of a spinocerebellar ataxia 13 in a patient presenting with a mutation in the KCNC3 gene.BMC neurology · 2023Article
- Basket to Purkinje Cell Inhibitory Ephaptic Coupling Is Abolished in Episodic Ataxia Type 1.Cells · 2023Article
- Suppression of Kv3.3 channels by antisense oligonucleotides reverses biochemical effects and motor impairment in spinocerebellar ataxia type 13 mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Transcranial direct current stimulation of cerebellum alters spiking precision in cerebellar cortex: A modeling study of cellular responses.PLoS computational biology · 2021Article
- Kv3.1 channelopathy: a novel loss-of-function variant and the mechanistic basis of its clinical phenotypes.Annals of translational medicine · 2021Article
- Article
- Cerebellar Kv3.3 potassium channels activate TANK-binding kinase 1 to regulate trafficking of the cell survival protein Hax-1.Nature communications · 2021Article
- BATTLE: Genetically Engineered Strategies for Split-Tunable Allocation of Multiple Transgenes in the Nervous System.iScience · 2020Article
- Loss-of-function BK channel mutation causes impaired mitochondria and progressive cerebellar ataxia.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Aberrant Cerebellar Circuitry in the Spinocerebellar Ataxias.Frontiers in neuroscience · 2020Review
- Cerebellar Development and Circuit Maturation: A Common Framework for Spinocerebellar Ataxias.Frontiers in neuroscience · 2020Review
- Review
- Motor Performances of Spontaneous and Genetically Modified Mutants with Cerebellar Atrophy.Cerebellum (London, England) · 2019Review
- Modeling Neurodegenerative Spinocerebellar Ataxia Type 13 in Zebrafish Using a Purkinje Neuron Specific Tunable Coexpression System.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Neurological Disease Modelling for Spinocerebellar Ataxia Using Zebrafish.Journal of experimental neuroscience · 2019Article
- C-terminal proline deletions in KCNC3 cause delayed channel inactivation and an adult-onset progressive SCA13 with spasticity.Cerebellum (London, England) · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cerebellum plays crucial roles in controlling sensorimotor functions. The neural output from the cerebellar cortex is transmitted solely by Purkinje cells (PCs), whose impairment causes cerebellar ataxia. Spinocerebellar ataxia type 13 (SCA13) is an autosomal dominant disease, and SCA13 patients exhibit cerebellar atrophy and cerebellar symptoms. Recent studies have shown that missense mutations in the voltage-gated K(+) channel Kv3.3 are responsible for SCA13. In the rodent brain, Kv3.3 mRNAs are expressed most strongly in PCs, suggesting that the mutations severely affect PCs in SCA13 patients. Nevertheless, how these mutations affect the function of Kv3.3 in PCs and, consequently, the morphology and neuronal excitability of PCs remains unclear. To address these questions, we used lentiviral vectors to express mutant mouse Kv3.3 (mKv3.3) channels harbouring an R424H missense mutation, which corresponds to the R423H mutation in the Kv3.3 channels of SCA13 patients, in mouse cerebellar cultures. The R424H mutant-expressing PCs showed decreased outward current density, broadened action potentials and elevated basal [Ca(2+)]i compared with PCs expressing wild-type mKv3.3 subunits or those expressing green fluorescent protein alone. Moreover, expression of R424H mutant subunits induced impaired dendrite development and cell death selectively in PCs, both of which were rescued by blocking P/Q-type Ca(2+) channels in the culture conditions. We therefore concluded that expression of R424H mutant subunits in PCs markedly affects the function of endogenous Kv3 channels, neuronal excitability and, eventually, basal [Ca(2+)]i, leading to cell death. These results suggest that PCs in SCA13 patients also exhibit similar defects in PC excitability and induced cell death, which may explain the pathology of SCA13.
Indexed as
Identifiers
What OpenQuestion holds
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.