ArticleHeart rhythm2016
Arrhythmogenic calmodulin mutations impede activation of small-conductance calcium-activated potassium current.
Article in Heart rhythm, 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, 30 citations in OpenAlex.
- Small-conductance CaThe Journal of physiology · 2026Review
- Antiarrhythmic effects of mirabegron on ventricular fibrillation in Langendorff-perfused rabbit ventricles.The Journal of physiology · 2025Article
- Oxidative stress-related genes in uveal melanoma: the role of CALM1 in modulating oxidative stress and apoptosis and its prognostic significance.Frontiers in oncology · 2025Article
- Calmodulin Mutations in Human Disease.Channels (Austin, Tex.) · 2023Review
- NaV1.6 dysregulation within myocardial T-tubules by D96V calmodulin enhances proarrhythmic sodium and calcium mishandling.The Journal of clinical investigation · 2023Article
- Distinct Molecular Features of NleG Type 3 Secreted Effectors Allow for Different Roles during Citrobacter rodentium Infection in Mice.Infection and immunity · 2023Article
- Long-term evolution of the epithelial cell secretome in preclinical 3D models of the human bronchial epithelium.Scientific reports · 2021Article
- Cardiac small-conductance calcium-activated potassium channels in health and disease.Pflugers Archiv : European journal of physiology · 2021Review
- Network Pharmacology-Based Strategy and Molecular Docking to Explore the Potential Mechanism of Jintiange Capsule for Treating Osteoporosis.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Different arrhythmia-associated calmodulin mutations have distinct effects on cardiac SK channel regulation.The Journal of general physiology · 2020Article
- Article
- Expression Profiles of Circular RNA in Human Atrial Fibrillation With Valvular Heart Diseases.Frontiers in cardiovascular medicine · 2020Article
- Impact of arrhythmogenic calmodulin variants on small conductance CaPhysiological reports · 2019Article
- Genetic Mosaicism in Calmodulinopathy.Circulation. Genomic and precision medicine · 2019Article
- Assessing predictions on fitness effects of missense variants in calmodulin.Human mutation · 2019Article
- The Crossroad of Ion Channels and Calmodulin in Disease.International journal of molecular sciences · 2019Review
- Ondansetron blocks wild-type and p.F503L variant small-conductance CaAmerican journal of physiology. Heart and circulatory physiology · 2018Article
- Small-conductance CaExperimental & molecular medicine · 2018Review
- Human Calmodulin Mutations.Frontiers in molecular neuroscience · 2018Article
- Calmodulinopathy: Functional Effects of CALM Mutations and Their Relationship With Clinical Phenotypes.Frontiers in cardiovascular medicine · 2018Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 5 countries.
Funding
Abstract
backgroundApamin-sensitive small-conductance calcium-activated potassium (SK) channels are gated by intracellular Ca(2+) through a constitutive interaction with calmodulin.
objectiveWe hypothesize that arrhythmogenic human calmodulin mutations impede activation of SK channels.
methodsWe studied 5 previously published calmodulin mutations (N54I, N98S, D96V, D130G, and F90L). Plasmids encoding either wild-type or mutant calmodulin were transiently transfected into human embryonic kidney 293 cells that stably express subtype 2 of SK protein channels (SK2 cells). Whole-cell voltage-clamp recording was used to determine apamin-sensitive current densities. We also performed optical mapping studies in normal murine hearts to determine the effects of apamin in hearts with (n=7) or without (n=3) pretreatment with sea anemone toxin.
resultsSK2 cells transfected with wild-type calmodulin exhibited an apamin-sensitive current density of 33.6 pA/pF (31.4-36.5 pA/pF) (median and confidence interval 25th-75th percentile), which was significantly higher than that observed for cells transfected with N54I (17.0 pA/pF [14.0-27.7 pA/pF]; P = .016), F90L (22.6 pA/pF [20.3-24.3 pA/pF]; P = .011), D96V (13.0 pA/pF [10.9-15.8 pA/pF]; P = .003), N98S (13.7 pA/pF [8.8-20.4 pA/pF]; P = .005), and D130G (17.6 pA/pF [13.8-24.6 pA/pF]; P = .003). The decrease in SK2 current densities was not associated with a decrease in membrane protein expression or intracellular distribution of the channel protein. Apamin increased the ventricular action potential duration at 80% repolarization (from 79.6 ms [63.4-93.3 ms] to 121.8 ms [97.9-127.2 ms]; P = .010) in hearts pretreated with anemone toxin but not in control hearts.
conclusionHuman arrhythmogenic calmodulin mutations impede the activation of SK2 channels in human embryonic kidney 293 cells.
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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.