BACKGROUND: Contractile dysfunction develops in the chronically instrumented canine myocardium after bouts of low-flow ischemia and persists after reperfusion. The objective of this study is to identify whether changes in the phosphorylation state of myosin-binding protein C (MyBP-C) are a potential cause of dysfunction. METHODS AND RESULTS: During low-flow ischemia, MyBP-C is dephosphorylated, and the number of actomyosin cross-bridges in the central core of the sarcomere decreases as thick filaments dissemble from the periphery of the myofibril. During reperfusion, MyBP-C remains dephosphorylated, and its degradation is accelerated. CONCLUSIONS: Dephosphorylation of MyBP-C may initiate changes in myofibril thick filament structure that decrease the interaction of myosin heads with actin thin filaments. Limiting the formation of actomyosin cross-bridges may contribute to the contractile dysfunction that is apparent after low-flow ischemia. Breakdown of MyBP-C during reperfusion may prolong myocardial stunning.
BACKGROUND:Contractile dysfunction develops in the chronically instrumented canine myocardium after bouts of low-flow ischemia and persists after reperfusion. The objective of this study is to identify whether changes in the phosphorylation state of myosin-binding protein C (MyBP-C) are a potential cause of dysfunction. METHODS AND RESULTS: During low-flow ischemia, MyBP-C is dephosphorylated, and the number of actomyosin cross-bridges in the central core of the sarcomere decreases as thick filaments dissemble from the periphery of the myofibril. During reperfusion, MyBP-C remains dephosphorylated, and its degradation is accelerated. CONCLUSIONS: Dephosphorylation of MyBP-C may initiate changes in myofibril thick filament structure that decrease the interaction of myosin heads with actin thin filaments. Limiting the formation of actomyosin cross-bridges may contribute to the contractile dysfunction that is apparent after low-flow ischemia. Breakdown of MyBP-C during reperfusion may prolong myocardial stunning.
Authors: Suresh Govindan; Diederik Wd Kuster; Brian Lin; Daniel J Kahn; Walter P Jeske; Jeanine M Walenga; Fred Leya; Debra Hoppensteadt; Jawed Fareed; Sakthivel Sadayappan Journal: Am J Cardiovasc Dis Date: 2013-06-10
Authors: Robert S Decker; Amy K Rines; Sakie Nakamura; Tejaswitha J Naik; J Andrew Wassertsrom; Hossein Ardehali Journal: Transl Res Date: 2010-01 Impact factor: 7.012
Authors: Sakthivel Sadayappan; Hanna Osinska; Raisa Klevitsky; John N Lorenz; Michelle Sargent; Jeffrey D Molkentin; Christine E Seidman; Jonathan G Seidman; Jeffrey Robbins Journal: Proc Natl Acad Sci U S A Date: 2006-10-30 Impact factor: 11.205
Authors: Euy-Myoung Jeong; Michelle M Monasky; Lianzhi Gu; Domenico M Taglieri; Bindiya G Patel; Hong Liu; Qiongying Wang; Ian Greener; Samuel C Dudley; R John Solaro Journal: J Mol Cell Cardiol Date: 2012-12-14 Impact factor: 5.000