| Molecular and functional evidence of HCN4 and caveolin-3 interaction during cardiomyocyte differentiation from human embryonic stem cells. | |
| | |
MedLine Citation:
|
PMID: 23311301 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Maturation of human embryonic stem cell-derived cardiomyocytes (hESC-CM) is accompanied by changes in ion channel expression, with relevant electrophysiological consequences. In rodent cardiomyocytes, the properties of HCN4, a major f-channel isoform, depends on 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 qPCR and immunocyto/histochemistry. F-current was measured in patch-clamped single cells. HCN4 and Cav3 co-localize in adult human atrial and ventricular CM, but not in fetal CM. Protein and mRNA for Cav3 were not detected in undifferentiated hESC, but expression increased during hESC-CM maturation. At 110 days, HCN4 appeared to be co-localized with Cav3. Voltage-dependent activation of the f-current was significantly more positive in fetal CM and 60-day hESC-CM (midpoint activation, V<sub>1/2</sub>, ~ -82mV) than in 110-day hESC-CM or adult CM (V<sub>1/2</sub> ~ -100mV). In the latter cells, caveolae disruption reversed voltage-dependence toward a more positive, or immature phenotype, with V<sub>1/2</sub> at -75mV, 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. |
| | |
Authors:
|
Alexis Bosman; Laura Sartiani; Valentina Spinelli; Martina Del Lungo; Francesca Stillitano; Daniele Nosi; Alessandro Mugelli; Elisabetta Cerbai; Marisa Jaconi |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2013-1-11 |
Journal Detail:
|
Title: Stem cells and development Volume: - ISSN: 1557-8534 ISO Abbreviation: Stem Cells Dev. Publication Date: 2013 Jan |
Date Detail:
|
Created Date: 2013-1-14 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101197107 Medline TA: Stem Cells Dev Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
University of Geneva, Pathology and Immunology, 1 rue Michel-Servet, Geneva 1211, Geneva, Geneva, Switzerland, 1211, +61432494777; alexis.bosman@unige.ch. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Temporal separation between CO(2) assimilation and growth? Experimental and theoretical evidence fro...
Next Document: Lymphatic filariasis in Papua New Guinea: distribution at district level and impact of mass drug adm...