ArticleStem cells and development2013
Molecular and functional evidence of HCN4 and caveolin-3 interaction during cardiomyocyte differentiation from human embryonic stem cells.
Article in Stem cells and development, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- The Contribution of HCN Channelopathies in Different Epileptic Syndromes, Mechanisms, Modulators, and Potential Treatment Targets: A Systematic Review.Frontiers in molecular neuroscience · 2022Pooled it
- Therapeutic role of caveolin family in stem cell fate and development for management of chronic degenerative diseases: A scientometric study to an in-depth review.Journal of advanced research · 2026Review
- Cardiac Cell Remodeling in Obesity and Diabetes.Handbook of experimental pharmacology · 2026Review
- Article
- Interleukin-6 Modulates the Expression and Function of HCN Channels: A Link Between Inflammation and Atrial Electrogenesis.International journal of molecular sciences · 2024Article
- Effect of Xenogeneic Substances on the Glycan Profiles and Electrophysiological Properties of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.International journal of stem cells · 2023Article
- A detailed characterization of the hyperpolarization-activated "funny" current (IPflugers Archiv : European journal of physiology · 2021Article
- Toward an in vitro human pacemaker.Pflugers Archiv : European journal of physiology · 2021Article
- Increased predominance of the matured ventricular subtype in embryonic stem cell-derived cardiomyocytes in vivo.Scientific reports · 2020Article
- Human iPSC modelling of a familial form of atrial fibrillation reveals a gain of function of If and ICaL in patient-derived cardiomyocytes.Cardiovascular research · 2020Article
- Absence of full-length dystrophin impairs normal maturation and contraction of cardiomyocytes derived from human-induced pluripotent stem cells.Cardiovascular research · 2020Article
- Optical Investigation of Action Potential and Calcium Handling Maturation of hiPSC-Cardiomyocytes on Biomimetic Substrates.International journal of molecular sciences · 2019Article
- Steps toward Maturation of Embryonic Stem Cell-Derived Cardiomyocytes by Defined Physical Signals.Stem cell reports · 2017Article
- Turning Potential Into Action: Using Pluripotent Stem Cells to Understand Heart Development and Function in Health and Disease.Stem cells translational medicine · 2017Article
- Damage-inducible intragenic demethylation of the human TP53 tumor suppressor gene is associated with transcription from an alternative intronic promoter.Molecular carcinogenesis · 2016Article
- Same-Single-Cell Analysis of Pacemaker-Specific Markers in Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Subtypes Classified by Electrophysiology.Stem cells (Dayton, Ohio) · 2016Article
- Interaction of Caveolin-3 and HCN is involved in the pathogenesis of diabetic cystopathy.Scientific reports · 2016Article
- HCN Channels Modulators: The Need for Selectivity.Current topics in medicinal chemistry · 2016Review
- Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation.Journal of visualized experiments : JoVE · 2015Article
- Signaling epicenters: the role of caveolae and caveolins in volatile anesthetic induced cardiac protection.Current pharmaceutical design · 2014Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Maturation of human embryonic stem cell-derived cardiomyocytes (hESC-CM) is accompanied by changes in ion channel expression, with relevant electrophysiological consequences. In rodent CM, the properties of hyperpolarization-activated cyclic nucleotide-gated channel (HCN)4, a major f-channel isoform, depends on the association with caveolin-3 (Cav3). To date, no information exists on changes in Cav3 expression and its associative relationship with HCN4 upon hESC-CM maturation. We hypothesize that Cav3 expression and its compartmentalization with HCN4 channels during hESC-CM maturation accounts for the progression of f-current properties toward adult phenotypes. To address this, hESC were differentiated into spontaneously beating CM and examined at ∼30, ∼60, and ∼110 days of differentiation. Human adult and fetal CM served as references. HCN4 and Cav3 expression and localization were analyzed by real time PCR and immunocyto/histochemistry. F-current was measured in patch-clamped single cells. HCN4 and Cav3 colocalize in adult human atrial and ventricular CM, but not in fetal CM. Proteins and mRNA for Cav3 were not detected in undifferentiated hESC, but expression increased during hESC-CM maturation. At 110 days, HCN4 appeared to be colocalized with Cav3. Voltage-dependent activation of the f-current was significantly more positive in fetal CM and 60-day hESC-CM (midpoint activation, V1/2, ∼ -82 mV) than in 110-day hESC-CM or adult CM (V1/2∼-100 mV). In the latter cells, caveolae disruption reversed voltage dependence toward a more positive or an immature phenotype, with V1/2 at -75 mV, while in fetal CM voltage dependence was not affected. Our data show, for the first time, a developmental change in HCN4-Cav3 association in hESC-CM. Cav3 expression and its association with ionic channels likely represent a crucial step of cardiac maturation.
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