ArticleThe Journal of biological chemistry2014
Channel-anchored protein kinase CK2 and protein phosphatase 1 reciprocally regulate KCNQ2-containing M-channels via phosphorylation of calmodulin.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Therapeutic potential of small molecules that block receptor-induced Kv7/M-current suppression in neuroprotection, seizures, and pain.British journal of pharmacology · 2026Article
- Oxytocinergic signalling in the respiratory parafacial region increases the activity of chemosensitive neurons and respiratory output.The Journal of physiology · 2025Article
- Case Report: A case of Poirier-Bienvenu neurodevelopmental syndrome manifesting primarily as eyelid myoclonia.Frontiers in pediatrics · 2025Article
- Casein Kinase 2 Affects Epilepsy by Regulating Ion Channels: A Potential Mechanism.CNS & neurological disorders drug targets · 2024Review
- Dehydroepiandrosterone Sulfate (DHEAS) Is an Endogenous Kv7 Channel Modulator That Reduces Kv7/M-Current Suppression and Inflammatory Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- The Okur-Chung Neurodevelopmental Syndrome Mutation CK2Frontiers in molecular biosciences · 2022Article
- Clinical and genetic analysis of six Chinese children with Poirier-Bienvenu neurodevelopmental syndrome caused by CSNK2B mutation.Neurogenetics · 2021Article
- An epilepsy-causing mutation leads to co-translational misfolding of the Kv7.2 channel.BMC biology · 2021Article
- Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels.Frontiers in molecular neuroscience · 2021Review
- Protein kinase CK2 and ion channels (Review).Biomedical reports · 2020Review
- Atomistic Insights of Calmodulin Gating of Complete Ion Channels.International journal of molecular sciences · 2020Review
- Phactr1 regulates Slack (KCNT1) channels via protein phosphatase 1 (PP1).FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- TwoFrontiers in physiology · 2020Article
- The Crossroad of Ion Channels and Calmodulin in Disease.International journal of molecular sciences · 2019Review
- Calmodulin: A Multitasking Protein in Kv7.2 Potassium Channel Functions.Biomolecules · 2018Review
- Lack of correlation between surface expression and currents in epileptogenic AB-calmodulin binding domain Kv7.2 potassium channel mutants.Channels (Austin, Tex.) · 2018Article
- M-current inhibition rapidly induces a unique CK2-dependent plasticity of the axon initial segment.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Calmodulin confers calcium sensitivity to the stability of the distal intracellular assembly domain of Kv7.2 channels.Scientific reports · 2017Article
- CK2 is a key regulator of SLC4A2-mediated ClPflugers Archiv : European journal of physiology · 2017Article
- Ethanol Withdrawal Drives Anxiety-Related Behaviors by Reducing M-type Potassium Channel Activity in the Lateral Habenula.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
M-type potassium channels, encoded by the KCNQ family genes (KCNQ2-5), require calmodulin as an essential co-factor. Calmodulin bound to the KCNQ2 subunit regulates channel trafficking and stabilizes channel activity. We demonstrate that phosphorylation of calmodulin by protein kinase CK2 (casein kinase 2) rapidly and reversibly modulated KCNQ2 current. CK2-mediated phosphorylation of calmodulin strengthened its binding to KCNQ2 channel, caused resistance to phosphatidylinositol 4,5-bisphosphate depletion, and increased KCNQ2 current amplitude. Accordingly, application of CK2-selective inhibitors suppressed KCNQ2 current. This suppression was prevented by co-expression of CK2 phosphomimetic calmodulin mutants or pretreatment with a protein phosphatase inhibitor, calyculin A. We also demonstrated that functional CK2 and protein phosphatase 1 (PP1) were selectively tethered to the KCNQ2 subunit. We identified a functional KVXF consensus site for PP1 binding in the N-terminal tail of KCNQ2 subunit: mutation of this site augmented current density. CK2 inhibitor treatment suppressed M-current in rat superior cervical ganglion neurons, an effect negated by overexpression of phosphomimetic calmodulin or pretreatment with calyculin A Furthermore, CK2 inhibition diminished the medium after hyperpolarization by suppressing the M-current. These findings suggest that CK2-mediated phosphorylation of calmodulin regulates the M-current, which is tonically regulated by CK2 and PP1 anchored to the KCNQ2 channel complex.
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