MUSCLE FATIGUE AND MUSCLE WEAKNESS: WHAT WE KNOW AND WHAT WE WISH WE DID Topic Editors P. Bryant Chase and Christina Karatzaferi PHYSIOLOGY FRONTIERS COPYRIGHT STATEMENT ABOUT FRONTIERS © Copyright 2007-2013 Frontiers is more than just an open-access publisher of scholarly articles: it is a pioneering Frontiers Media SA. All rights reserved. approach to the world of academia, radically improving the way scholarly research is managed. All content included on this site, The grand vision of Frontiers is a world where all people have an equal opportunity to seek, share such as text, graphics, logos, button and generate knowledge. Frontiers provides immediate and permanent online open access to all icons, images, video/audio clips, downloads, data compilations and its publications, but this alone is not enough to realize our grand goals. software, is the property of or is licensed to Frontiers Media SA (“Frontiers”) or its licensees and/or subcontractors. 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ISBN 978-2-88919-163-5 Find out more on how to host your own Frontiers Research Topic or contribute to one as an DOI 10.3389/978-2-88919-163-5 author by contacting the Frontiers Editorial Office: [email protected] Frontiers in Physiology August 2013 | Muscle fatigue and muscle weakness: what we know and what we wish we did | 1 MUSCLE FATIGUE AND MUSCLE WEAKNESS: WHAT WE KNOW AND WHAT WE WISH WE DID Topic Editors: P. Bryant Chase, Florida State University, USA Christina Karatzaferi, University of Thessaly, Greece The purpose of this Research Topic is to discuss evidence coming from macroscopic observations on the whole human/animal to investigations at the molecular level in an effort to identify critical factors in muscle fatigue and muscle weakness, in health and disease. Why is this important? Skeletal muscles confer movement to the human body using vast amounts of energy provided through complex metabolic pathways. Thus, whole body mobility and energy balance are dictated by muscle Image by P. Bryant Chase and Christina contraction. On the other side, muscle Karatzaferi. function reflects overall health status, as chronic conditions and/or ageing affect either or both of muscle quality (protein and fat content) and quantity (mass). In health, muscle fatigue is temporary and recovery occurs rapidly. In ageing or chronic disease however, muscle fatigue may occur prematurely and be persistent, endangering thus a person’s safety (i.e. weakness leads to falls), and leading the sufferer in a self-perpetuating vicious cycle of inactivity -> disuse muscle atrophy/metabolic disturbance and so on, that compounds morbidity (i.e. causing metabolic syndrome, fatness, hypertension, muscle cachexia) and that eventually leads to premature death. Frontiers in Physiology August 2013 | Muscle fatigue and muscle weakness: what we know and what we wish we did | 2 Research in skeletal muscle physiology and biophysics is at an exciting phase. The advent of new methodologies and technological advancements have allowed researchers to advance our knowledge on the “how’s” and “why’s” of muscle contraction – however there are still many unanswered questions especially when disease states are implicated. Such questions need addressing if as a scientific community we aspire to secure better designed interventions to improve muscle function, and thus improve quality of life and life prognosis for the ageing population and chronic disease patients. Frontiers in Physiology August 2013 | Muscle fatigue and muscle weakness: what we know and what we wish we did | 3 Table of Contents 05 Muscle Fatigue and Muscle Weakness: What We Know and What We Wish We Did Christina Karatzaferi and P. Bryant Chase Mechanisms of Muscle Function at the Sarcomeric Level 08 Recent Insights Into Muscle Fatigue at the Cross-Bridge Level Edward P. Debold 22 The Multiple Roles of Phosphate in Muscle Fatigue David G. Allen and Sofie Trajanovska 30 The Sarcomeric Protein Nebulin: Another Multifunctional Giant in Charge of Muscle Strength Optimization Coen A. C. Ottenheijm, Henk Granzier and Siegfried Labeit Modeling Muscle Function 39 A Physiologically Based, Multi-Scale Model of Skeletal Muscle Structure and Function O. Röhrle, J. B. Davidson and A. J. Pullan Physical Activity and Exercise Performance 53 Effects of Physical Activity and Inactivity on Muscle Fatigue Gregory C. Bogdanis 68 Antioxidants and Skeletal Muscle Performance: “Common Knowledge” vs. Experimental Evidence Andrés Hernández, Arthur Cheng and Håkan Westerblad The Muscle-Brain Connection of Fatigue in Health and Disease 74 Muscle Fatigue and Cognition: What is the Link? Tali Kobilo and Henriette van Praag 77 Hemodialysis Fatigue: Just “Simple” Fatigue or A Syndrome on Its Own Right? Giorgos K. Sakkas and Christina Karatzaferi 81 Fatigue is a Brain-Derived Emotion That Regulates the Exercise Behavior to Ensure the Protection of Whole Body Homeostasis Timothy David Noakes Frontiers in Physiology August 2013 | Muscle fatigue and muscle weakness: what we know and what we wish we did | 4 EDITORIAL published: 30 May 2013 doi: 10.3389/fphys.2013.00125 Muscle fatigue and muscle weakness: what we know and what we wish we did Christina Karatzaferi 1,2* and P.Bryant Chase 3 1 Department of Physical Education and Sports Science, University of Thessaly, Trikala, Greece 2 Department of Kinesiology, Center for Research and Technology Thessaly, Trikala, Greece 3 Department of Biological Science, The Florida State University, Tallahassee, FL, USA *Correspondence: [email protected] Edited by: Peter J. Reiser, Ohio State University, USA Reviewed by: Peter J. Reiser, Ohio State University, USA This Research Topic on muscle fatigue and muscle weakness 1996; Karatzaferi et al., 2003, 2008). These effects may be due presents the latest ideas, arguments, and evidence from investi- to direct binding to proteins, or due to a more global alteration gations at the molecular level to macroscopic observations on of cellular energetics (GATP )inthemyocyte(Karatzaferi et al., whole animals including humans, in an effort to identify criti- 2004). cal factors underlying fatigue and weakness in health and disease. In this Research Topic, Debold (2012) consolidates the most Skeletal muscles confer movement to the human body using recent information, including single molecule assays and molec- vast amounts of energy provided through complex metabolic ular biological approaches, about the mechanisms by which Pi, pathways such that whole body mobility and energy balance H+, and ADP inhibit actomyosin cross-bridge