ArticleHuman molecular genetics2017
Potassium channel dysfunction underlies Purkinje neuron spiking abnormalities in spinocerebellar ataxia type 2.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 67 citations in OpenAlex.
- Enhanced mGluR1 function causes motor deficits and region-specific Purkinje cell dysfunction.Brain : a journal of neurology · 2026Article
- Resilience to Endoplasmic Reticulum Stress Mitigates Membrane Hyperexcitability Underlying Late Disease Onset in a Murine Model of SCA6.Annals of neurology · 2026Article
- Cerebellar Purkinje cell firing reduction contributes to aging-related declining motor coordination in mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Autonomous STING signaling in Purkinje cells drives neurodegeneration independent of type I interferon.Cell reports · 2025Article
- Understanding the molecular diversity of synapses.Nature reviews. Neuroscience · 2025Review
- Spinocerebellar Ataxia Type 2: A Review and Personal Perspective.Neurology. Genetics · 2025Review
- Characterizing molecular and behavioral changes arising from ROMK potassium channel deficiency in the cerebellum.Frontiers in behavioral neuroscience · 2025Article
- Knockdown of the Non-canonical Wnt Gene Prickle2 Leads to Cerebellar Purkinje Cell Abnormalities While Cerebellar-Mediated Behaviors Remain Intact.Cerebellum (London, England) · 2024Article
- Targeting Ion Channels and Purkinje Neuron Intrinsic Membrane Excitability as a Therapeutic Strategy for Cerebellar Ataxia.Life (Basel, Switzerland) · 2023Review
- Viewpoint: spinocerebellar ataxias as diseases of Purkinje cell dysfunction rather than Purkinje cell loss.Frontiers in molecular neuroscience · 2023Review
- Deep Brain Stimulation of the Interposed Nucleus Reverses Motor Deficits and Stimulates Production of Anti-inflammatory Cytokines in Ataxia Mice.Molecular neurobiology · 2022Article
- Discovery of Novel Activators of Large-Conductance Calcium-Activated Potassium Channels for the Treatment of Cerebellar Ataxia.Molecular pharmacology · 2022Article
- Acute Cerebellar Inflammation and Related Ataxia: Mechanisms and Pathophysiology.Brain sciences · 2022Review
- KPhysiological reports · 2022Article
- Vulnerability of Human Cerebellar Neurons to Degeneration in Ataxia-Causing Channelopathies.Frontiers in systems neuroscience · 2022Review
- Rare KCND3 Loss-of-Function Mutation Associated With the SCA19/22.Frontiers in molecular neuroscience · 2022Article
- A novel, ataxic mouse model of ataxia telangiectasia caused by a clinically relevant nonsense mutation.eLife · 2021Article
- Clenbuterol-sensitive delayed outward potassium currents in a cell model of spinal and bulbar muscular atrophy.Pflugers Archiv : European journal of physiology · 2021Article
- Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity.Molecular psychiatry · 2021Article
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3 authors at 2 institutions in 1 country.
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Abstract
Alterations in Purkinje neuron firing often accompany ataxia, but the molecular basis for these changes is poorly understood. In a mouse model of spinocerebellar ataxia type 2 (SCA2), a progressive reduction in Purkinje neuron firing frequency accompanies cell atrophy. We investigated the basis for altered Purkinje neuron firing in SCA2. A reduction in the expression of large-conductance calcium-activated potassium (BK) channels and Kv3.3 voltage-gated potassium channels accompanies the inability of Purkinje neurons early in disease to maintain repetitive spiking. In association with prominent Purkinje neuron atrophy, repetitive spiking is restored, although at a greatly reduced firing frequency. In spite of a continued impairment in spike repolarization and a persistently reduced BK channel mediated afterhyperpolarization (AHP), repetitive spiking is maintained, through the increased activity of barium-sensitive potassium channels, most consistent with inwardly rectifying potassium (Kir) channels. Increased activity of Kir channels results in the generation of a novel AHP not seen in wild-type Purkinje neurons that also accounts for the reduced firing frequency late in disease. Homeostatic changes in Purkinje neuron morphology that help to preserve repetitive spiking can also therefore have deleterious consequences for spike frequency. These results suggest that the basis for spiking abnormalities in SCA2 differ depending on disease stage, and interventions targeted towards correcting potassium channel dysfunction in ataxia need to be tailored to the specific stage in the degenerative process.
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