Document Type
Article
Language
eng
Publication Date
11-2016
Publisher
American College of Sports Medicine
Source Publication
Medicine & Science in Sports & Exercise
Source ISSN
0195-9131
Original Item ID
DOI: 10.1249/MSS.0000000000001047
Abstract
The repeated intense stimulation of skeletal muscle rapidly decreases its force- and motion-generating capacity. This type of fatigue can be temporally correlated with the accumulation of metabolic by-products, including phosphate (Pi) and protons (H+). Experiments on skinned single muscle fibers demonstrate that elevated concentrations of these ions can reduce maximal isometric force, unloaded shortening velocity, and peak power, providing strong evidence for a causative role in the fatigue process. This seems to be due, in part, to their direct effect on muscle’s molecular motor, myosin, because in assays using isolated proteins, these ions directly inhibit myosin’s ability to move actin. Indeed, recent work using a single molecule laser trap assay has revealed the specific steps in the crossbridge cycle affected by these ions. In addition to their direct effects, these ions also indirectly affect myosin by decreasing the sensitivity of the myofilaments to calcium, primarily by altering the ability of the muscle regulatory proteins, troponin and tropomyosin, to govern myosin binding to actin. This effect seems to be partially due to fatigue-dependent alterations in the structure and function of specific subunits of troponin. Parallel efforts to understand the molecular basis of muscle contraction are providing new technological approaches that will allow us to gain unprecedented molecular detail of the fatigue process. This will be crucial to fully understand this ubiquitous phenomenon and develop appropriately targeted therapies to attenuate the debilitating effects of fatigue in clinical populations.
Recommended Citation
Debold, Edward Patrick; Fitts, Robert H.; Sundberg, Christopher W.; and Nosek, Thomas M., "Muscle Fatigue from the Perspective of a Single Crossbridge" (2016). Biological Sciences Faculty Research and Publications. 525.
https://epublications.marquette.edu/bio_fac/525
Comments
Accepted version. Medicine & Science in Sports & Exercise, Vol. 48, No. 11 (November 2016): 2270-2280. DOI. © 2016 American College of Sports Medicine. Used with permission.