Contractile properties of developing human fetal cardiac muscle

Racca, Alice W. and Klaiman, Jordan M. and Pioner, J. Manuel and Cheng, Yuanhua and Beck, Anita E. and Moussavi-Harami, Farid and Bamshad, Michael J. and Regnier, Michael (2015) Contractile properties of developing human fetal cardiac muscle. The Journal of Physiology, . n/a-n/a. ISSN 0022-3751. E-ISSN 1469-7793. (doi:https://doi.org/10.1113/JP271290) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://doi.org/10.1113/JP271290

Abstract

Abstract KEY POINTS: The contractile properties of human fetal cardiac muscle have not been previously studied. Small-scale approaches such as isolated myofibril and isolated contractile protein biomechanical assays allow study of activation and relaxation kinetics of human fetal cardiac muscle under well controlled conditions. We have examined the contractile properties of human fetal cardiac myofibrils and myosin across gestational age 59 days to 134 days. Human fetal cardiac myofibrils have low force and slow kinetics of activation and relaxation that increase during the time period studied, and kinetic changes may result from structural maturation and changes in protein isoform expression. Understanding the time course of human fetal cardiac muscle structure and contractile maturation can provide a framework to study development of contractile dysfunction with disease and evaluate the maturation state of cultured stem cell-derived cardiomyocytes. ABSTRACT: Little is known about the contractile properties of human fetal cardiac muscle during development. Understanding these contractile properties, and how they change throughout development, can provide valuable insight into human heart development, and provide a framework to study the early stages of cardiac diseases that develop in utero. We characterized the contractile properties of isolated human fetal cardiac myofibrils across 8-19 weeks of gestation. Mechanical measurements revealed that in early stages of gestation there is low specific force and slow rates of force development and relaxation, with increases in force and the rates of activation and relaxation as gestation progresses. The duration and slope of the initial, slow phase of relaxation, related to myosin detachment and thin filament deactivation rates, decreased with gestation age. F-actin sliding on human fetal cardiac myosin coated surfaces slowed significantly from 108 to 130 days gestation. Electron micrographs showed human fetal muscle myofibrils elongate and widen with age, but features such as the M-line and Z-band are apparent even as early as day 52. Protein isoform analysis revealed that ?-myosin is predominantly expressed even in the earliest time point studied, but there is a progressive increase in expression of cardiac troponin I (TnI), with a concomitant decrease in slow skeletal TnI. Together, our results suggest that cardiac myofibril force production and kinetics of activation and relaxation change significantly with gestation age and are influenced by the structural maturation of the sarcomere and changes in contractile filament protein isoforms. This article is protected by copyright. All rights reserved.

Item Type: Article
Uncontrolled keywords: fetal, human fetal, heart, cardiac, MYH6, MYH7, myofibril, muscle, Cardiac muscle, heart muscle, developing muscle, human development
Subjects: Q Science
Q Science > QM Human anatomy
Q Science > QP Physiology (Living systems) > QP517 Biochemistry
R Medicine
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: A.W. Racca
Date Deposited: 11 Jan 2016 14:39 UTC
Last Modified: 12 Jan 2016 15:23 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/53683 (The current URI for this page, for reference purposes)
  • Depositors only (login required):