Muscle Fatigue from the Perspective of a Single Crossbridge. Med Sci Sports Exerc 2016 Nov;48(11):2270-2280
Date
10/19/2016Pubmed ID
27434086DOI
10.1249/MSS.0000000000001047Scopus ID
2-s2.0-84978708650 (requires institutional sign-in at Scopus site) 69 CitationsAbstract
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.
Author List
Debold EP, Fitts RH, Sundberg CW, Nosek TMAuthors
Robert Fitts PhD Professor in the Biological Sciences department at Marquette UniversityChrisopher Sundberg in the CTSI department at Medical College of Wisconsin - CTSI
MESH terms used to index this publication - Major topics in bold
AcidosisCalcium
Humans
Hydrogen-Ion Concentration
Muscle Contraction
Muscle Fatigue
Muscle Fibers, Skeletal
Phosphates
