Document Type

Article

Language

eng

Format of Original

11 p.

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; PubMed Central: PMID: 27434086

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.

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.

Available for download on Wednesday, November 01, 2017

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