Friedreich's ataxia induced pluripotent stem cell-derived cardiomyocytes display electrophysiological abnormalities and calcium handling deficiency
AuthorCrombie, DE; Curl, CL; Raaijmakers, AJA; Sivakumaran, P; Kulkarni, T; Wong, RCB; Minami, I; Evans-Galea, MV; Lim, SY; Delbridge, L; ...
PublisherIMPACT JOURNALS LLC
University of Melbourne Author/sDelbridge, Leanne; Curl, Claire; Evans-Galea, Marguerite; Lim, Shiang; Delatycki, Martin; Pera, Martin; Pebay, Alice; Wong, Raymond; Crombie, Duncan; Dottori, Mirella; ...
AffiliationMedicine, Dentistry & Health Sciences
Melbourne Medical School
Eastern Hill Academic Centre
Surgery (St Vincent's)
Ophthalmology (Eye & Ear Hospital)
Melbourne School of Population and Global Health
School of Biomedical Sciences
Anatomy and Neuroscience
Chemical and Biomedical Engineering
Document TypeJournal Article
CitationsCrombie, D. E., Curl, C. L., Raaijmakers, A. J. A., Sivakumaran, P., Kulkarni, T., Wong, R. C. B., Minami, I., Evans-Galea, M. V., Lim, S. Y., Delbridge, L., Corben, L. A., Dottori, M., Nakatsuji, N., Trounce, I. A., Hewitt, A. W., Delatycki, M. B., Pera, M. F. & Pebay, A. (2017). Friedreich's ataxia induced pluripotent stem cell-derived cardiomyocytes display electrophysiological abnormalities and calcium handling deficiency. AGING-US, 9 (5), pp.1440-1452. https://doi.org/10.18632/aging.101247.
Access StatusAccess this item via the Open Access location
Open Access URLhttp://www.aging-us.com/article/101247/text
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472743
ARC Grant codeARC/FT140100047
We sought to identify the impacts of Friedreich's ataxia (FRDA) on cardiomyocytes. FRDA is an autosomal recessive degenerative condition with neuronal and non-neuronal manifestations, the latter including progressive cardiomyopathy of the left ventricle, the leading cause of death in FRDA. Little is known about the cellular pathogenesis of FRDA in cardiomyocytes. Induced pluripotent stem cells (iPSCs) were derived from three FRDA individuals with characterized GAA repeats. The cells were differentiated into cardiomyocytes to assess phenotypes. FRDA iPSC- cardiomyocytes retained low levels of FRATAXIN (FXN) mRNA and protein. Electrophysiology revealed an increased variation of FRDA- cardiomyocyte beating rates which was prevented by addition of nifedipine, suggestive of a calcium handling deficiency. Finally, calcium imaging was performed and we identified small amplitude, diastolic and systolic calcium transients confirming a deficiency in calcium handling. We defined a robust FRDA cardiac-specific electrophysiological profile in patient-derived iPSCs which could be used for high throughput compound screening. This cell-specific signature will contribute to the identification and screening of novel treatments for this life-threatening disease.
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- Medicine, Dentistry & Health Sciences Collected Works - Research Publications 
- Melbourne Medical School Collected Works - Research Publications 
- Eastern Hill Academic Centre - Research Publications 
- Surgery (St Vincent's) - Research Publications 
- Ophthalmology (Eye & Ear Hospital) - Research Publications 
- Paediatrics (RCH) - Research Publications 
- Melbourne School of Population and Global Health - Research Publications 
- School of Biomedical Sciences - Research Publications 
- Anatomy and Neuroscience - Research Publications 
- Physiology - Research Publications 
- Chemical and Biomedical Engineering - Research Publications 
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