ArticleAmerican journal of physiology. Heart and circulatory physiology2014
Sarcoplasmic reticulum Ca²⁺ release is both necessary and sufficient for SK channel activation in ventricular myocytes.
Article in American journal of physiology. Heart and circulatory physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 52 citations in OpenAlex.
- Local calcium dynamics and signalling in cardiomyocytes.Nature reviews. Cardiology · 2026Review
- Small-conductance CaThe Journal of physiology · 2026Review
- Pharmacological Enhancement of Small Conductance CaCirculation research · 2025Article
- Challenges in the Therapeutic Targeting of KCa Channels: From Basic Physiology to Clinical Applications.International journal of molecular sciences · 2024Review
- hiPSC-derived cardiomyocytes as a model to study the role of small-conductance CaFrontiers in cell and developmental biology · 2024Review
- Cardiac arrhythmogenesis: roles of ion channels and their functional modification.Frontiers in physiology · 2024Review
- Dual effects of the small-conductance CaAmerican journal of physiology. Heart and circulatory physiology · 2023Article
- Small-conductance calcium-activated potassium channels in the heart: expression, regulation and pathological implications.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Feedback contributions to excitation-contraction coupling in native functioning striated muscle.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Regulation of Papillary Muscle Contractility by NAD and Ammonia Interplay: Contribution of Ion Channels and Exchangers.Membranes · 2022Article
- Why Is Only Type 1 Electrocardiogram Diagnostic of Brugada Syndrome? Mechanistic Insights From Computer Modeling.Circulation. Arrhythmia and electrophysiology · 2022Article
- Effective termination of atrial fibrillation by SK channel inhibition is associated with a sudden organization of fibrillatory conduction.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2021Article
- Cardiac small-conductance calcium-activated potassium channels in health and disease.Pflugers Archiv : European journal of physiology · 2021Review
- The regulation of the small-conductance calcium-activated potassium current and the mechanisms of sex dimorphism in J wave syndrome.Pflugers Archiv : European journal of physiology · 2021Review
- Small-conductance CaHeart rhythm · 2020Article
- Transient receptor potential vanilloid-4 contributes to stretch-induced hypercontractility and time-dependent dysfunction in the aged heart.Cardiovascular research · 2020Article
- Impact of IBiophysical journal · 2020Article
- PKA phosphorylation underlies functional recruitment of sarcolemmal SK2 channels in ventricular myocytes from hypertrophic hearts.The Journal of physiology · 2020Article
- Inhibitory Effects of Dronedarone on Small Conductance Calcium Activated Potassium Channels in Patients with Chronic Atrial Fibrillation: Comparison to Amiodarone.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Small and Intermediate Calcium Activated Potassium Channels in the Heart: Role and Strategies in the Treatment of Cardiovascular Diseases.Frontiers in physiology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
SK channels are upregulated in human patients and animal models of heart failure (HF). However, their activation mechanism and function in ventricular myocytes remain poorly understood. We aim to test the hypotheses that activation of SK channels in ventricular myocytes requires Ca(2+) release from sarcoplasmic reticulum (SR) and that SK currents contribute to reducing triggered activity. SK2 channels were overexpressed in adult rat ventricular myocytes using adenovirus gene transfer. Simultaneous patch clamp and confocal Ca(2+) imaging experiments in SK2-overexpressing cells demonstrated that depolarizations resulted in Ca(2+)-dependent outward currents sensitive to SK inhibitor apamin. SR Ca(2+) release induced by rapid application of 10 mM caffeine evoked repolarizing SK currents, whereas complete depletion of SR Ca(2+) content eliminated SK currents in response to depolarizations, despite intact Ca(2+) influx through L-type Ca(2+) channels. Furthermore, voltage-clamp experiments showed that SK channels can be activated by global spontaneous SR Ca(2+) release events Ca(2+) waves (SCWs). Current-clamp experiments revealed that SK overexpression reduces the amplitude of delayed afterdepolarizations (DADs) resulting from SCWs and shortens action potential duration. Immunolocalization studies showed that overexpressed SK channels are distributed both at external sarcolemmal membranes and along the Z-lines, resembling the distribution of endogenous SK channels. In summary, SR Ca(2+) release is both necessary and sufficient for the activation of SK channels in rat ventricular myocytes. SK currents contribute to repolarization during action potentials and attenuate DADs driven by SCWs. Thus SK upregulation in HF may have an anti-arrhythmic effect by reducing triggered activity.
Indexed as
Identifiers
What OpenQuestion holds
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.