title: Eccentric contraction: unraveling mechanisms of force enhancement and energy conservation.
abstract: During the past century, physiologists have made steady progress in elucidating the molecular mechanisms of muscle contraction. However, this progress has so far failed to definitively explain the high force and low energy cost of eccentric muscle contraction. Hypotheses that have been proposed to explain increased muscle force during active stretch include cross-bridge mechanisms, sarcomere and half-sarcomere length non-uniformity, and engagement of a structural element upon muscle activation. The available evidence suggests that force enhancement results from an interaction between an elastic element in muscle sarcomeres, which is engaged upon activation, and the cross-bridges, which interact with the elastic elements to regulate their length and stiffness. Similarities between titin-based residual force enhancement in vertebrate muscle and twitchin-based 'catch' in invertebrate muscle suggest evolutionary homology. The winding filament hypothesis suggests plausible molecular mechanisms for effects of both Ca(2+) influx and cross-bridge cycling on titin in active muscle. This hypothesis proposes that the N2A region of titin binds to actin upon Ca(2+) influx, and that the PEVK region of titin winds on the thin filaments during force development because the cross-bridges not only translate but also rotate the thin filaments. Simulations demonstrate that a muscle model based on the winding filament hypothesis can predict residual force enhancement on the descending limb of the length-tension curve in muscles during eccentric contraction. A kinematic model of titin winding based on sarcomere geometry makes testable predictions about titin isoforms in different muscles. Ongoing research is aimed at testing these predictions and elucidating the biochemistry of the underlying protein interactions.
authors.affiliation: Northern Arizona University, Department of Biological Sciences and Center for Bioengineering Innovation, Flagstaff, AZ 86011-4165, USA kiisa.nishikawa@nau.edu.
authors.forename: Kiisa
authors.initials: K
authors.lastname: Nishikawa
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D064211:Connectin / Q000737:chemistry / Q000378:metabolism; D004734:Energy Metabolism; D006801:Humans; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology*; D012518:Sarcomeres / Q000502:physiology
chemical_list: D064211:Connectin
keywords: Active stretch; Energy efficiency; Titin activation; Winding filament hypothesis