ArticlePloS one2013
A change in configuration of the calmodulin-KCNQ channel complex underlies Ca2+-dependent modulation of KCNQ channel activity.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 61 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
- Biosafety and efficacy of Kv7 activating rdHSV-CA8∗ analgesic gene therapy for chronic pain via the intra-articular route in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Disease-modifying rdHSV-CA8* non-opioid analgesic gene therapy treats chronic osteoarthritis pain by activating Kv7 voltage-gated potassium channels.Frontiers in molecular neuroscience · 2024Article
- rdHSV-CA8 non-opioid analgesic gene therapy decreases somatosensory neuronal excitability by activating Kv7 voltage-gated potassium channels.Frontiers in molecular neuroscience · 2024Article
- 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
- Involvement of CaCellular and molecular neurobiology · 2023Article
- Redox regulation of KeLife · 2023Article
- Signaling pathways involved in NMDA-induced suppression of M-channels in corticotropin-releasing hormone neurons in central amygdala.Journal of neurochemistry · 2022Article
- Paradoxical neuronal hyperexcitability in a mouse model of mitochondrial pyruvate import deficiency.eLife · 2022Article
- PIPCommunications biology · 2021Article
- An epilepsy-causing mutation leads to co-translational misfolding of the Kv7.2 channel.BMC biology · 2021Article
- Kv7 Channels and Excitability Disorders.Handbook of experimental pharmacology · 2021Article
- Identifying mutation hotspots reveals pathogenetic mechanisms of KCNQ2 epileptic encephalopathy.Scientific reports · 2020Article
- PIPInternational journal of molecular sciences · 2020Article
- Inhibition of M/KFrontiers in molecular neuroscience · 2020Article
- M-Current Suppression, Seizures and Lipid Metabolism: A Potential Link Between Neuronal Kv7 Channel Regulation and Dietary Therapies for Epilepsy.Frontiers in physiology · 2020Review
- Pharmacological Manipulation of KFrontiers in physiology · 2020Review
- KCNQs: Ligand- and Voltage-Gated Potassium Channels.Frontiers in physiology · 2020Review
- TwoFrontiers in physiology · 2020Article
- The S2-S3 Loop of Kv7.4 Channels Is Essential for Calmodulin Regulation of Channel Activation.Frontiers in physiology · 2020Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
All subtypes of KCNQ channel subunits (KCNQ1-5) require calmodulin as a co-factor for functional channels. It has been demonstrated that calmodulin plays a critical role in KCNQ channel trafficking as well as calcium-mediated current modulation. However, how calcium-bound calmodulin suppresses the M-current is not well understood. In this study, we investigated the molecular mechanism of KCNQ2 current suppression mediated by calcium-bound calmodulin. We show that calcium induced slow calmodulin dissociation from the KCNQ2 channel subunit. In contrast, in homomeric KCNQ3 channels, calcium facilitated calmodulin binding. We demonstrate that this difference in calmodulin binding was due to the unique cysteine residue in the KCNQ2 subunit at aa 527 in Helix B, which corresponds to an arginine residue in other KCNQ subunits including KCNQ3. In addition, a KCNQ2 channel associated protein AKAP79/150 (79 for human, 150 for rodent orthologs) also preferentially bound calcium-bound calmodulin. Therefore, the KCNQ2 channel complex was able to retain calcium-bound calmodulin either through the AKPA79/150 or KCNQ3 subunit. Functionally, increasing intracellular calcium by ionomycin suppressed currents generated by KCNQ2, KCNQ2(C527R) or heteromeric KCNQ2/KCNQ3 channels to an equivalent extent. This suggests that a change in the binding configuration, rather than dissociation of calmodulin, is responsible for KCNQ current suppression. Furthermore, we demonstrate that KCNQ current suppression was accompanied by reduced KCNQ affinity toward phosphatidylinositol 4,5-bisphosphate (PIP2) when assessed by a voltage-sensitive phosphatase, Ci-VSP. These results suggest that a rise in intracellular calcium induces a change in the configuration of CaM-KCNQ binding, which leads to the reduction of KCNQ affinity for PIP2 and subsequent current suppression.
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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.