ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2013
Microglial SK3 and SK4 currents and activation state are modulated by the neuroprotective drug, riluzole.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Riluzole shifts glial responses to protect synapses and memory in Aβ oligomer-treated rats.Journal of neuroinflammation · 2026Article
- LMNA Deficiency Reveals a Role for SK3 Channel Dysfunction in Atrioventricular Block.JACC. Clinical electrophysiology · 2026Article
- Uncovering immune cell-associated genes in breast cancer: based on summary data-based Mendelian randomized analysis and colocalization study.Breast cancer research : BCR · 2024Article
- The Physio-Pathological Role of Group I Metabotropic Glutamate Receptors Expressed by Microglia in Health and Disease with a Focus on Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2023Review
- Cure of Alzheimer's Dementia Requires Addressing All of the Affected Brain Cell Types.Journal of clinical medicine · 2023Article
- Supplementary Pharmacotherapy for the Behavioral Abnormalities Caused by Stressors in Humans, Focused on Post-Traumatic Stress Disorder (PTSD).Journal of clinical medicine · 2023Article
- Formulating treatment of major psychiatric disorders: algorithm targets the dominantly affected brain cell-types.Discover mental health · 2023Review
- Identification of an immune-related gene prognostic index for predicting prognosis, immunotherapeutic efficacy, and candidate drugs in amyotrophic lateral sclerosis.Frontiers in cellular neuroscience · 2022Article
- Ion Channels Orchestrate Pancreatic Ductal Adenocarcinoma Progression and Therapy.Frontiers in pharmacology · 2020Review
- Review of Clinical Studies Targeting Inflammatory Pathways for Individuals With Autism.Frontiers in psychiatry · 2019Review
- Comparing Effects of Transforming Growth Factor β1 on Microglia From Rat and Mouse: Transcriptional Profiles and Potassium Channels.Frontiers in cellular neuroscience · 2018Article
- Microglia Responses to Pro-inflammatory Stimuli (LPS, IFNγ+TNFα) and Reprogramming by Resolving Cytokines (IL-4, IL-10).Frontiers in cellular neuroscience · 2018Article
- Responses of rat and mouse primary microglia to pro- and anti-inflammatory stimuli: molecular profiles, KJournal of neuroinflammation · 2017Article
- Checkpoints to the Brain: Directing Myeloid Cell Migration to the Central Nervous System.International journal of molecular sciences · 2016Review
- Molecular and Cellular Responses to Interleukin-4 Treatment in a Rat Model of Transient Ischemia.Journal of neuropathology and experimental neurology · 2016Article
- Complex molecular and functional outcomes of single versus sequential cytokine stimulation of rat microglia.Journal of neuroinflammation · 2016Article
- KCa3.1/IK1 Channel Regulation by cGMP-Dependent Protein Kinase (PKG) via Reactive Oxygen Species and CaMKII in Microglia: An Immune Modulating Feedback System?Frontiers in immunology · 2015Article
- PKA reduces the rat and human KCa3.1 current, CaM binding, and Ca2+ signaling, which requires Ser332/334 in the CaM-binding C terminus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- T-type channels buddy up.Pflugers Archiv : European journal of physiology · 2014Review
- Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Microglia monitor the CNS for 'danger' signals after acute injury, such as stroke and trauma, and then undergo complex activation processes. Classical activation of microglia can produce neurotoxic levels of glutamate and immune mediators (e.g., pro-inflammatory cytokines, reactive oxygen and nitrogen species), while alternative activation up-regulates anti-inflammatory molecules and is thought to resolve inflammation and protect the brain. Thus, pharmacological strategies to decrease classical- and/or promote alternative activation are of interest. Here, we assessed actions of the neuroprotective drug, riluzole, on two Ca(2+)- activated K channels in microglia - SK3 (KCa2.3, KCNN3) and SK4 (KCa3.1, KCNN4) - and on classical versus alternative microglial activation. Riluzole is used to treat amyotrophic lateral sclerosis, and is in clinical trials for several other CNS disorders, where it has been presumed to target neurons and reduce glutamate-mediated toxicity. We show that simply elevating intracellular Ca(2+) to micromolar levels in whole-cell recordings does not activate SK channels in a cell line derived from primary rat microglia (MLS-9). In intact cells, riluzole raised cytoplasmic Ca(2+), but it was marginal (~200 nM) and transient (2 min). Surprisingly then, in whole cell recordings, riluzole rapidly activated SK3 and SK4 channels for as long as it was present, and did not require elevated intracellular Ca(2+). We then used primary rat microglia to analyze expression of several activation markers and inflammatory mediators. Riluzole decreased classical LPS-induced activation, and increased some aspects of IL-4-induced alternative activation. These actions on microglia suggest an additional mechanism underlying the neuroprotective actions of riluzole.
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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.