Developmental changes in cardiomyocytes differentiated from human embryonic stem cells: a molecular and electrophysiological approach

Autor: Marisa Jaconi, Elisabetta Cerbai, Laura Sartiani, Francesca Stillitano, Alessandro Mugelli, Esther Bettiol
Rok vydání: 2007
Předmět:
Potassium Channels
Time Factors
Calcium Channels
L-Type
RNA
Messenger/genetics/metabolism
Cellular differentiation
Cyclic Nucleotide-Gated Cation Channels
ddc:616.07
Biology
Models
Biological
Pacemaker potential
Mice
Myocytes
Cardiac/ cytology/ metabolism
Diastole
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Myocyte
Animals
Humans
Myocytes
Cardiac
RNA
Messenger
Potassium Channels
Inwardly Rectifying
Cells
Cultured
Embryonic Stem Cells
Calcium Channels
L-Type/metabolism
Potassium Channels
Inwardly Rectifying/metabolism
Developmental maturation
Inward-rectifier potassium ion channel
Potassium Channels/genetics/metabolism
Cell Differentiation
Cell Biology
Anatomy
Embryonic stem cell
Potassium channel
Cell biology
Electrophysiology
Gene Expression Regulation
Embryonic Stem Cells/ cytology/ metabolism
Molecular Medicine
Intracellular
Developmental Biology
Zdroj: Stem Cells, Vol. 25, No 5 (2007) pp. 1136-1144
ISSN: 1066-5099
Popis: Cardiomyocytes derived from human embryonic stem cells constitute a promising cell source for the regeneration of damaged hearts. The assessment of their in vitro functional properties is mandatory to envisage appropriate cardiac cell-based therapies. In this study, we characterized human embryonic stem cell-derived cardiomyocytes over a 3-month period, using patch-clamp or intracellular recordings to assess their functional maturation and reverse transcriptase-polymerase chain reaction to evaluate the expression of ion channel-encoding subunits. Ito1 and IK1, the transient outward and inward rectifier potassium currents, were present in cardiomyocytes only, whereas the rapid delayed rectifier potassium current (IKr), pacemaker current (If), and L-type calcium current (ICa,L) could be recorded both in undifferentiated human embryonic stem cells and in cardiomyocytes. Most of the currents underwent developmental maturation in cardiomyocytes, as assessed by modifications in current density (Ito1, IK1, and ICa,L) and properties (If). Ion-channel mRNAs were always present when the current was recorded. Intracellular recordings in spontaneously beating clusters of cardiomyocytes revealed changes in action potential parameters and in response to pharmacological tools according to time of differentiation. In summary, human embryonic stem cell-derived cardiomyocytes mature over time during in vitro differentiation, approaching an adult phenotype. Disclosure of potential conflicts of interest is found at the end of this article.
Databáze: OpenAIRE
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