Document Detail


Modeling Timothy syndrome with iPS cells.
MedLine Citation:
PMID:  23299782     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Genetic mutations in ion channel genes that are associated with cardiac arrhythmias have been identified over the past several decades. However, little is known about the pathophysiological processes. An important limitation has been the difficulty of using human cardiomyocytes to study arrhythmias and identify drugs. To circumvent this issue, we have developed a method using human-induced pluripotent stem cells to generate cardiomyocytes from individuals with Timothy syndrome (TS), a genetic disorder characterized by QT prolongation, ventricular tachycardia, and autism. The TS ventricular-like cardiomyocytes exhibit deficits in contraction, electrical signaling, and calcium handling, as revealed by live cell imaging and electrophysiological studies. We tested candidate drugs in TS cardiomyocytes and found that roscovitine could successfully rescue these cellular phenotypes. The use of a human cellular model of cardiac arrhythmias provides a useful new platform not only to study disease mechanisms but also to develop new therapies to treat cardiac arrhythmias.
Authors:
Masayuki Yazawa; Ricardo E Dolmetsch
Publication Detail:
Type:  Journal Article     Date:  2013-01-09
Journal Detail:
Title:  Journal of cardiovascular translational research     Volume:  6     ISSN:  1937-5395     ISO Abbreviation:  J Cardiovasc Transl Res     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-16     Completed Date:  2013-07-02     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  101468585     Medline TA:  J Cardiovasc Transl Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1-9     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Action Potentials
Anti-Arrhythmia Agents / pharmacology
Calcium Channels, L-Type / drug effects,  genetics,  metabolism*
Calcium Signaling
Cell Line
Genetic Predisposition to Disease
Humans
Induced Pluripotent Stem Cells / drug effects,  metabolism*
Kinetics
Long QT Syndrome / drug therapy,  genetics,  metabolism*,  physiopathology
Mutation
Myocardial Contraction
Myocytes, Cardiac / drug effects,  metabolism*
Phenotype
Purines / pharmacology
Syndactyly / drug therapy,  genetics,  metabolism*,  physiopathology
Grant Support
ID/Acronym/Agency:
DP1 OD003889/OD/NIH HHS; K99 HL111345/HL/NHLBI NIH HHS; R00 HL111345/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/CACNA1C protein, human; 0/Calcium Channels, L-Type; 0/Purines; 0/roscovitine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Optical imaging with a high-resolution microendoscope to identify cholesteatoma of the middle ear.
Next Document:  Novel Vasodilators in Heart Failure.