ArticleCell death and differentiation2016
Activation of SK2 channels preserves ER Ca²⁺ homeostasis and protects against ER stress-induced cell death.
Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 53 citations in OpenAlex.
- A New Potassium Channel on the Endoplasmic Reticulum Membrane in a Rat Brain: Electropharmacology and Molecular Evidence.Basic and clinical neuroscience · 2025Article
- Disruption of ovarian function and induction of apoptosis in female mice by Brefeldin A: Mechanistic insights into reproductive toxicity.Animal models and experimental medicine · 2025Article
- Inhibitor-based modulation of huntingtin aggregation mechanisms mitigates fibril-induced cellular stress.Nature communications · 2025Article
- Butyrolactone-I from Marine Fungal Metabolites Mitigates Heat-Stress-Induced Apoptosis in IPEC-J2 Cells and Mice Through the ROS/PERK/CHOP Signaling Pathway.Marine drugs · 2024Article
- Plasma membrane SK2 channel activity regulates migration and chemosensitivity of high-grade serous ovarian cancer cells.Molecular oncology · 2024Article
- Trpv6 channel targeting using monoclonal antibody induces prostate cancer cell apoptosis and tumor regression.Cell death & disease · 2024Article
- The mitochondrial quality control system: a new target for exercise therapeutic intervention in the treatment of brain insulin resistance-induced neurodegeneration in obesity.International journal of obesity (2005) · 2024Review
- SK-Channel Activation Alters Peripheral Metabolic Pathways in Mice, but Not Lipopolysaccharide-Induced Fever or Inflammation.Journal of inflammation research · 2022Article
- Apamin as a BBB Shuttle and Its Effects on T Cell Population During the Experimental Autoimmune Encephalomyelitis-Induced Model of Multiple Sclerosis.Neurotoxicity research · 2021Article
- Differential modulation of SK channel subtypes by phosphorylation.Cell calcium · 2021Article
- Dichotomic Hippocampal Transcriptome After Glutamatergic vs. GABAergic Deletion of the Cannabinoid CB1 Receptor.Frontiers in synaptic neuroscience · 2021Article
- Pharmacological modulation of mitochondrial ion channels.British journal of pharmacology · 2019Review
- Misfolded proinsulin impairs processing of precursor of insulin receptor and insulin signaling in β cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Parkinson's disease-associated LRRK2-G2019S mutant acts through regulation of SERCA activity to control ER stress in astrocytes.Acta neuropathologica communications · 2019Article
- Translocation Associated Membrane Protein 1 Contributes to Chronic Constriction Injury-Induced Neuropathic Pain in the Dorsal Root Ganglion and Spinal Cord in Rats.Journal of molecular neuroscience : MN · 2018Article
- SK channel activation is neuroprotective in conditions of enhanced ER-mitochondrial coupling.Cell death & disease · 2018Article
- The role of CaCell calcium · 2018Review
- Altered NMDA receptor-evoked intracellular CaThe Journal of physiology · 2017Article
- SK2 channels regulate mitochondrial respiration and mitochondrial CaCell death and differentiation · 2017Article
- Glucose-regulated protein 75 determines ER-mitochondrial coupling and sensitivity to oxidative stress in neuronal cells.Cell death discovery · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alteration of endoplasmic reticulum (ER) Ca(2+) homeostasis leads to excessive cytosolic Ca(2+) accumulation and delayed neuronal cell death in acute and chronic neurodegenerative disorders. While our recent studies established a protective role for SK channels against excessive intracellular Ca(2+) accumulation, their functional role in the ER has not been elucidated yet. We show here that SK2 channels are present in ER membranes of neuronal HT-22 cells, and that positive pharmacological modulation of SK2 channels with CyPPA protects against cell death induced by the ER stressors brefeldin A and tunicamycin. Calcium imaging of HT-22 neurons revealed that elevated cytosolic Ca(2+) levels and decreased ER Ca(2+) load during sustained ER stress could be largely prevented by SK2 channel activation. Interestingly, SK2 channel activation reduced the amount of the unfolded protein response transcription factor ATF4, but further enhanced the induction of CHOP. Using siRNA approaches we confirmed a detrimental role for ATF4 in ER stress, whereas CHOP regulation was dispensable for both, brefeldin A toxicity and CyPPA-mediated protection. Cell death induced by blocking Ca(2+) influx into the ER with the SERCA inhibitor thapsigargin was not prevented by CyPPA. Blocking the K(+) efflux via K(+)/H(+) exchangers with quinine inhibited CyPPA-mediated neuroprotection, suggesting an essential role of proton uptake and K(+) release in the SK channel-mediated neuroprotection. Our data demonstrate that ER SK2 channel activation preserves ER Ca(2+) uptake and retention which determines cell survival in conditions where sustained ER stress contributes to progressive neuronal death.
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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.