Please use this identifier to cite or link to this item:
https://hdl.handle.net/10356/84027
Title: | A post-MI power struggle: adaptations in cardiac power occur at the sarcomere level alongside MyBP-C and RLC phosphorylation | Authors: | Toepfer, Christopher N. Sikkel, Markus B. Caorsi, Valentina Vydyanath, Anupama Torre, Iratxe Copeland, O'Neal Lyon, Alexander R. Marston, Steven B. Luther, Pradeep K. Macleod, Kenneth T. West, Timothy G. Ferenczi, Michael Alan |
Keywords: | contractile function infarction |
Issue Date: | 2016 | Source: | Toepfer, C. N., Sikkel, M. B., Caorsi, V., Vydyanath, A., Torre, I., Copeland, O., et al. (2016). A post-MI power struggle: adaptations in cardiac power occur at the sarcomere level alongside MyBP-C and RLC phosphorylation. American Journal of Physiology - Heart and Circulatory Physiology, 311(2), H465-H475. | Series/Report no.: | American Journal of Physiology - Heart and Circulatory Physiology | 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. | URI: | https://hdl.handle.net/10356/84027 http://hdl.handle.net/10220/41594 |
ISSN: | 0363-6135 | DOI: | 10.1152/ajpheart.00899.2015 | Schools: | Lee Kong Chian School of Medicine (LKCMedicine) | Organisations: | Lee Kong Chian School of Medicine | Rights: | © 2016 The American Physiological Society. This is the author created version of a work that has been peer reviewed and accepted for publication by American Journal of Physiology - Heart and Circulatory Physiology, The American Physiological Society. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1152/ajpheart.00899.2015]. | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | LKCMedicine Journal Articles |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
A post-MI power struggle- adaptations in cardiac power occur at the sarcomere level alongside MyBP-C and RLC phosphorylation.pdf | 2.72 MB | Adobe PDF | View/Open |
SCOPUSTM
Citations
50
7
Updated on Mar 24, 2024
Web of ScienceTM
Citations
20
7
Updated on Oct 29, 2023
Page view(s) 20
649
Updated on Mar 28, 2024
Download(s) 50
120
Updated on Mar 28, 2024
Google ScholarTM
Check
Altmetric
Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.