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      In Vivo Sarcomere Lengths Become More Non-uniform upon Activation in Intact Whole Muscle

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          Abstract

          The sarcomere force-length relationship has been extensively used to predict muscle force potential. The common practice is to measure the mean sarcomere length (SL) in a relaxed muscle at a single location and at a given length, and this mean SL is assumed to represent the SLs at other locations across the muscle. However, in a previous study, we found that SLs are highly non-uniform across an intact passive muscle. Moreover, SL non-uniformity increases during activation in single myofibril experiments. Myofibrils lack some structural proteins that comprise an intact muscle, and therefore, the increased SL dispersion upon activation seen in myofibrils may not occur in intact whole muscle. The objectives of the current study were (i) to measure the distribution of SLs in an activated intact muscle; and (ii) to assess the feasibility of using the mean SL measured at a specific location of the muscle to predict muscle force. Using state-of-the-art multi-photon microscopy and a miniature tendon force transducer, in vivo sarcomeres in the mouse tibialis anterior were imaged simultaneously with muscle force during isometric tetanic contractions. We found that in vivo SL dispersion increased substantially during activation and reached average differences of ~1.0 μm. These differences in SL are associated with theoretical force differences of 70–100% of the maximal isometric force. Furthermore, SLs measured at a single location in the passive muscle were poor predictors of active force potential. Although mean SLs in the activated muscle were better predictors of force potential, predicted forces still differed by as much as 35% from the experimentally measured maximal isometric forces.

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          Most cited references40

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          The variation in isometric tension with sarcomere length in vertebrate muscle fibres

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            Variational inference for Dirichlet process mixtures

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              The effects of length and stimulus rate on tension in the isometric cat soleus muscle.

              1. By subdividing ventral roots and supplying stimulating pulses to different groups of motor units in rotation, smooth contractions of soleus could be obtained with low rates of stimulation.2. Isometric tension was recorded with different rates of stimulation, and at different muscle lengths.3. Longitudinal histological sections were cut from muscles fixed at different lengths, and sarcomeres were measured. Mean sarcomere lengths in soleus could then be related to the angle at the ankle.4. At high rates of stimulation the maximum active tension was obtained at a length corresponding to an angle of about 60 degrees at the ankle, and a mean sarcomere length of about 2.8 mu. The isometric tension fell only slightly on shortening the muscle to a length equivalent to 100 degrees , and a mean sarcomere length about 2.3 mu. Further shortening caused a marked fall in tension.5. There was a reciprocal relationship between stimulus rate and muscle length; when the muscle was long low rates of stimulation gave near maximal tension, whereas at short lengths the maximum tension was reached only when the stimulus rate was very high. It is suggested that stimulating pulses activate the contractile machinery of the muscle more effectively at long than at short muscle lengths.6. When at low rates of stimulation pulses were distributed among the motor units in rotation to give a smooth contraction, the tension rose higher than during the unfused tetanus that accompanied synchronous stimulation of the same motor units at the same rate. It is suggested that in an unfused tetanus internal movement of the muscle reduces the tension below that developed in a truly isometric state.7. The rate of rise of tension in an isometric tetanus varied with both muscle length and rate of stimulation. At each stimulus rate there was a range of lengths in which the isometric tension developed slowly, this was the same length range in which, at that stimulus rate, the length tension curve was steep.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                07 December 2017
                2017
                : 8
                : 1015
                Affiliations
                Human Performance Laboratory, Faculty of Kinesiology, University of Calgary , Calgary, AB, Canada
                Author notes

                Edited by: Julian Stelzer, Case Western Reserve University, United States

                Reviewed by: Dennis R. Claflin, University of Michigan, United States; John Jeshurun Michael, Cornell University, United States

                *Correspondence: Walter Herzog wherzog@ 123456ucalgary.ca

                This article was submitted to Striated Muscle Physiology, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2017.01015
                5725405
                29270135
                c09b7aff-5949-4a6e-b51e-ed5ea36d6004
                Copyright © 2017 Moo, Leonard and Herzog.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 September 2017
                : 23 November 2017
                Page count
                Figures: 9, Tables: 0, Equations: 4, References: 43, Pages: 12, Words: 7682
                Funding
                Funded by: Alberta Innovates - Health Solutions 10.13039/501100000145
                Award ID: 10013510
                Funded by: Canadian Institutes of Health Research 10.13039/501100000024
                Award ID: 10010953
                Funded by: Killam Trusts 10.13039/501100004073
                Funded by: Natural Sciences and Engineering Research Council of Canada 10.13039/501100000038
                Funded by: Canada Research Chairs 10.13039/501100001804
                Categories
                Physiology
                Original Research

                Anatomy & Physiology
                second harmonic generation microscopy,active contraction,in vivo,non-uniformity,force-length relationship,skeletal muscle properties,sarcomere instability

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