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001-es BibID:BIBFORM079019
035-os BibID:(absztrakt azonosító)3076-Pos Board B284 (WoS)000430563300097
Első szerző:Jian, Zhong
Cím:Mechanical Load Effects on Cardiomyocyte Action Potential, Cacium Transient, and Contraction Revealed by using a Novel Patch-Clamp-in-Gel Technology / Zhong Jian, Yi-je Chen, Bence Hegyi, Tamas Banyasz, Zana Coulibaly, Rafael Shimkunas, Nipavan Chiamvimonvat, Kit S. Lam, Leighton T. Izu, Ye Chen-Izu
Dátum:2018
ISSN:0006-3495
Megjegyzések:Background: In every heartbeat, cardiomyocytes are under mechanical load when the heart pumps blood against peripheral resistance. However, because previous patch-clamp experiments are mostly done using load-free cells, the mechanical load effects on cells were precluded. Method: We have developed an innovative Patch-Clamp-in-Gel technique which enables us to patch-clamp cardiomyocytes while they are embedded in a viscoelastic 3-D hydrogel that imposes a controlled mechanical load on cells. Results: We performed Patch-Clamp-in-Gel experiments using mouse ventricular myocytes and discovered the following major results. (1) Compared to load-free cells, the myocytes in-gel under mechanical load show prolonged action potential (AP), early afterdepolarization (EAD), delayed afterdepolarization (DAD) and triggered AP, suggesting that mechanical load significantly increases arrhythmogenic AP activities. (2) Simultaneous triple-signal recordings of AP, Ca2+, and contraction further reveal that load-induced EAD occurs independently while load-induced DAD occurs in conjunction with spontaneous Ca2+ tide and contraction. (3) The above load-induced changes can be reversed by specific inhibition of the nitric oxide synthase 1 (NOS1 or nNOS), demonstrating a critical role of nNOS in mediating the mechanotransduction pathway. Conclusion: Our newly developed Patch-Clamp-in-Gel technology provides a powerful tool to control mechanical load on single cells for studying mechanotransduction effects on ion channels, action potential, Ca2+ signaling, and myocyte contraction. We found that mechanical load significantly affects the three dynamic systems - electrical, Ca2+ signaling, and contractile systems - that govern cardiac function and arrhythmogenic activities, and nNOS-NO signaling mediates the mechanotransduction in cardiomyocytes.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idézhető absztrakt
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Megjelenés:Biophysical Journal. - 114 : 3 (2018), p. 620a. -
További szerzők:Chen, Yi-Je Hegyi Bence (1987-) (élettanász) Bányász Tamás (1960-) (élettanász) Coulibaly, Zana Shimkunas, Rafael Chiamvimonvat, Nipavan Lam, Kit S. Izu, Leighton T. Chen-Izu, Ye
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