ArticleProceedings of the National Academy of Sciences of the United States of America2013
SK4 Ca2+ activated K+ channel is a critical player in cardiac pacemaker derived from human embryonic stem cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 70 citations in OpenAlex.
- Intermediate Conductance Calcium-Activated Potassium Channel Activation in Stem Cell Antigen-1 Positive Cells Contributed to Vascular Restenosis.Journal of the American Heart Association · 2026Article
- The SK4 channel allosteric blocker, BA6b9, reduces atrial fibrillation substrate in rats with reduced ejection fraction.PNAS nexus · 2024Article
- M2 macrophage‑derived exosomes alleviate KCa3.1 channel expression in rapidly paced HL‑1 myocytes via the NF‑κB (p65)/STAT3 signaling pathway.Molecular medicine reports · 2024Article
- A single coiled-coil domain mutation in hIKCa channel subunits disrupts preferential formation of heteromeric hSK1:hIKCa channels.The European journal of neuroscience · 2024Article
- Stem cell-derived cardiomyocytes expressing a dominant negative pacemaker HCN4 channel do not reduce the risk of graft-related arrhythmias.Frontiers in cardiovascular medicine · 2024Article
- Neuron-oligodendroglial interactions in health and malignant disease.Nature reviews. Neuroscience · 2023Review
- Understanding Arrhythmogenic Cardiomyopathy: Advances through the Use of Human Pluripotent Stem Cell Models.Genes · 2023Review
- What makes the sinoatrial node tick? A question not for the faint of heart.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- 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
- Novel insights in the pathomechanism of Brugada syndrome and fever-related type 1 ECG changes in a preclinical study using human-induced pluripotent stem cell-derived cardiomyocytes.Clinical and translational medicine · 2023Article
- cAMP-PKA signaling modulates the automaticity of human iPSC-derived cardiomyocytes.The Journal of general physiology · 2023Article
- Regulation of Papillary Muscle Contractility by NAD and Ammonia Interplay: Contribution of Ion Channels and Exchangers.Membranes · 2022Article
- Allosteric inhibitors targeting the calmodulin-PIP2 interface of SK4 KProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Blockade of SK4 channels suppresses atrial fibrillation by attenuating atrial fibrosis in canines with prolonged atrial pacing.International journal of medical sciences · 2022Article
- Proton-modulated interactions of ions with transport sites of prokaryotic and eukaryotic NCX prototypes.Cell calcium · 2021Article
- Role of intermediate-conductance calcium-activated potassium channels in atrial fibrillation in canines with rapid atrial pacing.Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing · 2021Article
- Pharmacologic Approach to Sinoatrial Node Dysfunction.Annual review of pharmacology and toxicology · 2021Review
- Inhibition of KCa3.1 Channels Suppresses Atrial Fibrillation via the Attenuation of Macrophage Pro-inflammatory Polarization in a Canine Model With Prolonged Rapid Atrial Pacing.Frontiers in cardiovascular medicine · 2021Article
- Nucleoside Diphosphate Kinase B Contributes to Arrhythmogenesis in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes from a Patient with Arrhythmogenic Right Ventricular Cardiomyopathy.Journal of clinical medicine · 2020Article
- Cardiac Pacemaker Activity and Aging.Annual review of physiology · 2020Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. Two main mechanisms have been proposed: (i) the "voltage-clock," where the hyperpolarization-activated funny current If causes diastolic depolarization that triggers action potential cycling; and (ii) the "Ca(2+) clock," where cyclical release of Ca(2+) from Ca(2+) stores depolarizes the membrane during diastole via activation of the Na(+)-Ca(2+) exchanger. Nonetheless, these mechanisms remain controversial. Here, we used human embryonic stem cell-derived cardiomyocytes (hESC-CMs) to study their autonomous beating mechanisms. Combined current- and voltage-clamp recordings from the same cell showed the so-called "voltage and Ca(2+) clock" pacemaker mechanisms to operate in a mutually exclusive fashion in different cell populations, but also to coexist in other cells. Blocking the "voltage or Ca(2+) clock" produced a similar depolarization of the maximal diastolic potential (MDP) that culminated by cessation of action potentials, suggesting that they converge to a common pacemaker component. Using patch-clamp recording, real-time PCR, Western blotting, and immunocytochemistry, we identified a previously unrecognized Ca(2+)-activated intermediate K(+) conductance (IK(Ca), KCa3.1, or SK4) in young and old stage-derived hESC-CMs. IK(Ca) inhibition produced MDP depolarization and pacemaker suppression. By shaping the MDP driving force and exquisitely balancing inward currents during diastolic depolarization, IK(Ca) appears to play a crucial role in human embryonic cardiac automaticity.
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