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- 저자 : ( Misuk Kang1 ) (검색결과 1 건)
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Endothelin Receptor Overexpression Alters Diastolic Function in Cultured Rat Ventricular Myocytes
( Misuk Kang1 ),( Jeffery W. Walker ),( Ka Young Chung ) 한국응용약물학회 2012 Biomolecules & Therapeutics(구 응용약물학회지) Vol.20 No.4
The endothelin (ET) signaling pathway controls many physiological processes in myocardium and often becomes upregulated in heart diseases. The aim of the present study was to investigate the effects of ET receptor upregulation on the contractile function of adult ventricular myocytes. Primary cultured adult rat ventricular myocytes were used as a model system of ET receptor overexpression in the heart. Endothelin receptor type A (ETA) or type B (ETB) was overexpressed by Adenoviral infection, and the twitch responses of infected ventricular myocytes were measured after ET-1 stimulation. Overexpression of ETA exaggerated positive inotropic effect (PIE) and diastolic shortening of ET-1, and induced a new twitch response including twitch broadening. On the contrary, overexpression of ETB increased PIE of ET-1, but did not affect other two twitch responses. Control myocytes expressing endogenous receptors showed a parallel increase in twitch amplitude and systolic Ca2+ in response to ET-1. However, intracellular Ca2+ did not change in proportion to the changes in contractility in myocytes overexpressing ETA. Overexpression of ETA enhanced both systolic and diastolic contractility without parallel changes in Ca2+. Differential regulation of this nature indicates that upregulation of ETA may contribute to diastolic myocardial dysfunction by selectively targeting myofi lament proteins that regulate resting cell length, twitch duration and responsiveness to prevailing Ca2+.
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