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• W2034010143 endingPage "H2399" @default.
• W2034010143 startingPage "H2391" @default.
• W2034010143 abstract "Endothelin (ET)-1 regulates the contractility and growth of the heart by binding G protein-coupled receptors of the ET type A receptor (ET A )/ET type B (ET B ) receptor family. ET A , the predominant ET-1 receptor subtype in myocardium, is thought to localize preferentially within cardiac T tubules, but the consequences of mislocalization are not fully understood. Here we examined the effects of the overexpression of ET A in conjunction with T-tubule loss in cultured adult rat ventricular myocytes. In adult myocytes cultured for 3 to 4 days, the normally robust positive inotropic effect (PIE) of ET-1 was lost in parallel with T-tubule degeneration and a decline in ET A protein levels. In these T tubule-compromised myocytes, an overexpression of ET A using an adenoviral vector did not rescue the responsiveness to ET-1, despite the robust expression in the surface sarcolemma. The inclusion of the actin polymerization inhibitor cytochalasin D (CD) during culture prevented gross morphological changes including a loss of T tubules and a rounding of intercalated discs, but CD alone did not rescue the responsiveness to ET-1 or prevent ET A downregulation. The rescue of a normal PIE in 3- to 4-day cultured myocytes required both an increased expression of ET A and intact T tubules (preserved with CD). Therefore, the activation of ET A localized in T tubules was associated with a strong PIE, whereas the activation of ET A in surface sarcolemma was not. The results provide insight into the pathological cardiac conditions in which ET A is upregulated and T-tubule morphology is altered." @default.
• W2034010143 created "2016-06-24" @default.
• W2034010143 creator A5007872868 @default.
• W2034010143 creator A5079184638 @default.
• W2034010143 creator A5083183654 @default.
• W2034010143 date "2008-05-01" @default.
• W2034010143 modified "2023-09-23" @default.
• W2034010143 title "Contractile regulation by overexpressed ET_Arequires intact T tubules in adult rat ventricular myocytes" @default.
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• W2034010143 doi "https://doi.org/10.1152/ajpheart.00011.2008" @default.
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