ArticleCell death & disease2014
Subcellular expression and neuroprotective effects of SK channels in human dopaminergic neurons.
Article in Cell death & disease, 2014. 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, 76 citations in OpenAlex.
- SK3 channel and mitochondrial ROS mediate NADPH oxidase-independent NETosis induced by calcium influx.Proceedings of the National Academy of Sciences of the United States of America · 2015Trial
- Magnesium Ions as Modulators of Voltage-Gated and Ligand-Gated Ion Channels in Central Neurons.International journal of molecular sciences · 2025Review
- Ferroptosis inhibition protects against α-synuclein-related neuronal cell death.Cell death & disease · 2025Article
- Repurposing the memory-promoting meclofenoxate hydrochloride as a treatment for Parkinson's disease through integrative multi-omics analysis.NPJ Parkinson's disease · 2025Article
- Inhibitor-based modulation of huntingtin aggregation mechanisms mitigates fibril-induced cellular stress.Nature communications · 2025Article
- CACNA1A haploinsufficiency leads to reduced synaptic function and increased intrinsic excitability.Brain : a journal of neurology · 2025Article
- Article
- VTA dopamine neurons are hyperexcitable in 3xTg-AD mice due to casein kinase 2-dependent SK channel dysfunction.Nature communications · 2024Article
- Plasma membrane SK2 channel activity regulates migration and chemosensitivity of high-grade serous ovarian cancer cells.Molecular oncology · 2024Article
- The raphe nuclei are the early lesion site of gastricActa pharmaceutica Sinica. B · 2024Article
- Challenges in the Therapeutic Targeting of KCa Channels: From Basic Physiology to Clinical Applications.International journal of molecular sciences · 2024Review
- KCNN1 promotes proliferation and metastasis of breast cancer via ERLIN2-mediated stabilization and K63-dependent ubiquitination of Cyclin B1.Carcinogenesis · 2023Article
- Negative modulation of mitochondrial calcium uniporter complex protects neurons against ferroptosis.Cell death & disease · 2023Article
- VTA dopamine neurons are hyperexcitable in 3xTg-AD mice due to casein kinase 2-dependent SK channel dysfunction.bioRxiv : the preprint server for biology · 2023Article
- CaMolecules (Basel, Switzerland) · 2023Review
- Inhibition of SK Channels in VTA Affects Dopaminergic Neurons to Improve the Depression-Like Behaviors of Post-Stroke Depression Rats.Neuropsychiatric disease and treatment · 2023Article
- Enhanced firing of locus coeruleus neurons and SK channel dysfunction are conserved in distinct models of prodromal Parkinson's disease.Scientific reports · 2022Article
- Alternative Targets for Modulators of Mitochondrial Potassium Channels.Molecules (Basel, Switzerland) · 2022Review
- Differential modulation of SK channel subtypes by phosphorylation.Cell calcium · 2021Article
- A Parkinson's Disease-relevant Mitochondrial and Neuronal Morphology High-throughput Screening Assay in LUHMES Cells.Bio-protocol · 2021Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small-conductance Ca(2+)-activated K(+) channel activation is an emerging therapeutic approach for treatment of neurological diseases, including stroke, amyotrophic lateral sclerosis and schizophrenia. Our previous studies showed that activation of SK channels exerted neuroprotective effects through inhibition of NMDAR-mediated excitotoxicity. In this study, we tested the therapeutic potential of SK channel activation of NS309 (25 μM) in cultured human postmitotic dopaminergic neurons in vitro conditionally immortalized and differentiated from human fetal mesencephalic cells. Quantitative RT-PCR and western blotting analysis showed that differentiated dopaminergic neurons expressed low levels of SK2 channels and high levels of SK1 and SK3 channels. Further, protein analysis of subcellular fractions revealed expression of SK2 channel subtype in mitochondrial-enriched fraction. Mitochondrial complex I inhibitor rotenone (0.5 μM) disrupted the dendritic network of human dopaminergic neurons and induced neuronal death. SK channel activation reduced mitochondrial membrane potential, while it preserved the dendritic network, cell viability and ATP levels after rotenone challenge. Mitochondrial dysfunction and delayed dopaminergic cell death were prevented by increasing and/or stabilizing SK channel activity. Overall, our findings show that activation of SK channels provides protective effects in human dopaminergic neurons, likely via activation of both membrane and mitochondrial SK channels. Thus, SK channels are promising therapeutic targets for neurodegenerative disorders such as Parkinson's disease, where dopaminergic cell loss is associated with progression of the disease.
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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.