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Electrophysiology of hiPSC-Cardiomyocytes Co-Cultured with HEK Cells Expressing the Inward Rectifier Channel
- Source :
- International Journal of Molecular Sciences, Volume 22, Issue 12, International Journal of Molecular Sciences, Vol 22, Iss 6621, p 6621 (2021)
- Publication Year :
- 2021
-
Abstract
- The immature electrophysiology of human-induced pluripotent stem cell-derived cardiomyocytes (hiCMs) complicates their use for therapeutic and pharmacological purposes. An insufficient inward rectifying current (IK1) and the presence of a funny current (if) cause spontaneous electrical activity. This study tests the hypothesis that the co-culturing of hiCMs with a human embryonic kidney (HEK) cell-line expressing the Kir2.1 channel (HEK-IK1) can generate an electrical syncytium with an adult-like cardiac electrophysiology. The mechanical activity of co-cultures using different HEK-IK1:hiCM ratios was compared with co-cultures using wildtype (HEK–WT:hiCM) or hiCM alone on days 3–8 after plating. Only ratios of 1:3 and 1:1 showed a significant reduction in spontaneous rate at days 4 and 6, suggesting that IK1 was influencing the electrophysiology. Detailed analysis at day 4 revealed an increased incidence of quiescent wells or sub-areas. Electrical activity showed a decreased action potential duration (APD) at 20% and 50%, but not at 90%, alongside a reduced amplitude of the aggregate AP signal. A computational model of the 1:1 co-culture replicates the electrophysiological effects of HEK–WT. The addition of the IK1 conductance reduced the spontaneous rate and APD20, 50 and 90, and minor variation in the intercellular conductance caused quiescence. In conclusion, a 1:1 co-culture HEK-IK1:hiCM caused changes in electrophysiology and spontaneous activity consistent with the integration of IK1 into the electrical syncytium. However, the additional electrical effects of the HEK cell at 1:1 increased the possibility of electrical quiescence before sufficient IK1 was integrated into the syncytium.
- Subjects :
- 0301 basic medicine
IK1
QH301-705.5
Induced Pluripotent Stem Cells
030204 cardiovascular system & hematology
Giant Cells
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
0302 clinical medicine
Humans
Myocytes, Cardiac
Biology (General)
Physical and Theoretical Chemistry
Potassium Channels, Inwardly Rectifying
QD1-999
Molecular Biology
Spectroscopy
Syncytium
HEK
Inward-rectifier potassium ion channel
Cardiac electrophysiology
Chemistry
maturation
Organic Chemistry
HEK 293 cells
Wild type
hiCMs
General Medicine
electrophysiology
Embryonic stem cell
co-culture
Myocardial Contraction
Coculture Techniques
Computer Science Applications
Cell biology
Electrophysiology
030104 developmental biology
HEK293 Cells
Intracellular
Subjects
Details
- ISSN :
- 14220067 and 16616596
- Volume :
- 22
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- International journal of molecular sciences
- Accession number :
- edsair.doi.dedup.....9f10c5527b0b318b5343f41b550e745b