Skip to main content

Contractility and kinetics of human fetal and human adult skeletal muscle

Racca, Alice W., Beck, Anita E., Rao, Vijay S., Flint, Galina V., Lundy, Scott D., Born, Donald E., Bamshad, Michael J., Regnier, Michael (2013) Contractility and kinetics of human fetal and human adult skeletal muscle. The Journal of Physiology, 591 (12). pp. 3049-3061. ISSN 0022-3751. E-ISSN 1469-7793. (doi:10.1113/jphysiol.2013.252650) (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/jphysiol.2013.252650

Abstract

Little is known about the contraction and relaxation properties of fetal skeletal muscle, and measurements thus far have been made with non-human mammalian muscle. Data on human fetal skeletal muscle contraction are lacking, and there are no published reports on the kinetics of either fetal or adult human skeletal muscle myofibrils. Understanding the contractile properties of human fetal muscle would be valuable in understanding muscle development and a variety of muscle diseases that are associated with mutations in fetal muscle sarcomere proteins. Therefore, we characterised the contractile properties of developing human fetal skeletal muscle and compared them to adult human skeletal muscle and rabbit psoas muscle. Electron micrographs showed human fetal muscle sarcomeres are not fully formed but myofibril formation is visible. Isolated myofibril mechanical measurements revealed much lower specific force, and slower rates of isometric force development, slow phase relaxation, and fast phase relaxation in human fetal when compared to human adult skeletal muscle. The duration of slow phase relaxation was also significantly longer compared to both adult groups, but was similarly affected by elevated ADP. F-actin sliding on human fetal skeletal myosin coated surfaces in in vitro motility (IVM) assays was much slower compared with adult rabbit skeletal myosin, though the Km(app) (apparent (fitted) Michaelis-Menten constant) of F-actin speed with ATP titration suggests a greater affinity of human fetal myosin for nucleotide binding. Replacing ATP with 2 deoxy-ATP (dATP) increased F-actin speed for both groups by a similar amount. Titrations of ADP into IVM assays produced a similar inhibitory affect for both groups, suggesting ADP binding may be similar, at least under low load. Together, our results suggest slower but similar mechanisms of myosin chemomechanical transduction for human fetal muscle that may also be limited by immature myofilament structure.

Item Type: Article
DOI/Identification number: 10.1113/jphysiol.2013.252650
Uncontrolled keywords: MYH3, myofibril, in vitro motility, human development, human skeletal muscle, skeletal, embryonic myosin
Subjects: Q Science > QP Physiology (Living systems)
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: A.W. Racca
Date Deposited: 11 Jan 2016 14:44 UTC
Last Modified: 29 May 2019 16:52 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/53686 (The current URI for this page, for reference purposes)
  • Depositors only (login required):