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A post-MI power struggle: adaptations in cardiac power occur at the sarcomere level alongside MyBP-C and RLC phosphorylation.

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Title: A post-MI power struggle: adaptations in cardiac power occur at the sarcomere level alongside MyBP-C and RLC phosphorylation.
Authors: Toepfer, CN
Sikkel, MB
Caorsi, V
Vydyanath, A
Torre, I
Copeland, O
Lyon, AR
Marston, SB
Luther, PK
MacLeod, KT
West, TG
Ferenczi, MA
Item Type: Journal Article
Abstract: Myocardial remodeling in response to chronic myocardial infarction (CMI) progresses through two phases, hypertrophic compensation and congestive decompensation. Nothing is known about the ability of uninfarcted myocardium to produce force, velocity, and power during these clinical phases, even though adaptation in these regions likely drives progression of compensation. We hypothesized that enhanced cross-bridge-level contractility underlies mechanical compensation and is controlled in part by changes in the phosphorylation states of myosin regulatory proteins. We induced CMI in rats by left anterior descending coronary artery ligation. We then measured mechanical performance in permeabilized ventricular trabecula taken distant from the infarct zone and assayed myosin regulatory protein phosphorylation in each individual trabecula. During full activation, the compensated myocardium produced twice as much power and 31% greater isometric force compared with noninfarcted controls. Isometric force during submaximal activations was raised >2.4-fold, while power was 2-fold greater. Electron and confocal microscopy demonstrated that these mechanical changes were not a result of increased density of contractile protein and therefore not an effect of tissue hypertrophy. Hence, sarcomere-level contractile adaptations are key determinants of enhanced trabecular mechanics and of the overall cardiac compensatory response. Phosphorylation of myosin regulatory light chain (RLC) increased and remained elevated post-MI, while phosphorylation of myosin binding protein-C (MyBP-C) was initially depressed but then increased as the hearts became decompensated. These sensitivities to CMI are in accordance with phosphorylation-dependent regulatory roles for RLC and MyBP-C in crossbridge function and with compensatory adaptation in force and power that we observed in post-CMI trabeculae.
Issue Date: 27-May-2016
Date of Acceptance: 24-May-2016
URI: http://hdl.handle.net/10044/1/34272
DOI: https://dx.doi.org/10.1152/ajpheart.00899.2015
ISSN: 0363-6135
Publisher: American Physiological Society
Start Page: H465
End Page: H475
Journal / Book Title: American Journal of Physiology - Heart and Circulatory Physiology
Volume: 311
Issue: 2
Copyright Statement: © 2015, American Journal of Physiology - Heart and Circulatory Physiology
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 092852/Z/10/Z
Keywords: contractile apparatus
contractile function
infarction
myosin binding protein C
regulatory light chain
Cardiovascular System & Hematology
0606 Physiology
1116 Medical Physiology
Publication Status: Published
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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