ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
PKA reduces the rat and human KCa3.1 current, CaM binding, and Ca2+ signaling, which requires Ser332/334 in the CaM-binding C terminus.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
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- Kcnn4/KCa3.1 inhibition blunts polycystic kidney disease progression in mouse models.JCI insight · 2025Article
- Vasoactive intestinal peptide excites GnRH neurons via KCa3.1, a potential player in the slow afterhyperpolarization current.Frontiers in cellular neuroscience · 2024Article
- Article
- Functional Potassium Channels in Macrophages.The Journal of membrane biology · 2023Review
- Regulatory role of KCa3.1 in immune cell function and its emerging association with rheumatoid arthritis.Frontiers in immunology · 2022Review
- Insulin-Induced Cardiomyocytes Hypertrophy That Is Prevented by Taurine via β-alanine-Sensitive NaNutrients · 2021Article
- ATP-evoked intracellular CaJournal of neuroinflammation · 2021Article
- The Molecular Basis for the Calcium-Dependent Slow Afterhyperpolarization in CA1 Hippocampal Pyramidal Neurons.Frontiers in physiology · 2021Review
- Targeting microglia L-type voltage-dependent calcium channels for the treatment of central nervous system disorders.Journal of neuroscience research · 2021Review
- CaMKK2 is inactivated by cAMP-PKA signaling and 14-3-3 adaptor proteins.The Journal of biological chemistry · 2020Article
- A Compartmentalized Reduction in Membrane-Proximal Calmodulin Reduces the Immune Surveillance Capabilities of CD8Frontiers in pharmacology · 2020Article
- Small and Intermediate Calcium Activated Potassium Channels in the Heart: Role and Strategies in the Treatment of Cardiovascular Diseases.Frontiers in physiology · 2020Review
- Protein Kinase A-Mediated Suppression of the Slow Afterhyperpolarizing KCa3.1 Current in Temporal Lobe Epilepsy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Nucleus accumbens shell small conductance potassium channels underlie adolescent ethanol exposure-induced anxiety.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- Targeting Adenosine in Cancer Immunotherapy to Enhance T-Cell Function.Frontiers in immunology · 2019Review
- Purinergic signaling in oligodendrocyte development and function.Journal of neurochemistry · 2018Review
- Comparing Effects of Transforming Growth Factor β1 on Microglia From Rat and Mouse: Transcriptional Profiles and Potassium Channels.Frontiers in cellular neuroscience · 2018Article
- Structure, Gating and Basic Functions of the Ca2+-activated K Channel of Intermediate Conductance.Current neuropharmacology · 2018Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Ca(2+)-dependent K(+) channel, KCa3.1 (KCNN4/IK/SK4), is widely expressed and contributes to cell functions that include volume regulation, migration, membrane potential, and excitability. KCa3.1 is now considered a therapeutic target for several diseases, including CNS disorders involving microglial activation; thus, we need to understand how KCa3.1 function is regulated. KCa3.1 gating and trafficking require calmodulin binding to the two ends of the CaM-binding domain (CaMBD), which also contains three conserved sites for Ser/Thr kinases. Although cAMP protein kinase (PKA) signaling is important in many cells that use KCa3.1, reports of channel regulation by PKA are inconsistent. We first compared regulation by PKA of native rat KCa3.1 channels in microglia (and the microglia cell line, MLS-9) with human KCa3.1 expressed in HEK293 cells. In all three cells, PKA activation with Sp-8-Br-cAMPS decreased the current, and this was prevented by the PKA inhibitor, PKI14-22. Inhibiting PKA with Rp-8-Br-cAMPS increased the current in microglia. Mutating the single PKA site (S334A) in human KCa3.1 abolished the PKA-dependent regulation. CaM-affinity chromatography showed that CaM binding to KCa3.1 was decreased by PKA-dependent phosphorylation of S334, and this regulation was absent in the S334A mutant. Single-channel analysis showed that PKA decreased the open probability in wild-type but not S334A mutant channels. The same decrease in current for native and wild-type expressed KCa3.1 channels (but not S334A) occurred when PKA was activated through the adenosine A2a receptor. Finally, by decreasing the KCa3.1 current, PKA activation reduced Ca(2+)-release-activated Ca(2+) entry following activation of metabotropic purinergic receptors in microglia.
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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.