Titin Hysteresis is Greater for Actively Lengthened Compared to Passively Lengthened Skeletal Muscle Sarcomeres

2313-Pos Board B450 Titin Hysteresis is Greater for Actively Lengthened Compared to Passively Lengthened Skeletal Muscle Sarcomeres Jens Herzog, Timothy R. Leonard, Azim Jinha, Walter Herzog. Kinesiology, University of Calgary, Calgary, AB, Canada. Titin is a giant protein found in skeletal muscle which behaves mechanically like a molecular spring. The extensible region of titin within the sarcomere contains spring-like domains arranged in series with stiffness and visco-elastic properties which come into play in an orderly fashion with increasing sarcomere length. When lengthened within the physiologically relevant range of sarcomere excursion, first the Ig domains align, followed by stretching of the PEVK region. Beyond the physiological range, Ig domains unfold, and this unfolding is thought to be highly visco-elastic. Active muscle lengthened from 1.8 to 4.0mm and to beyond myofilament overlap (> 4.0mm) will produce more force than passively lengthened muscle at the same sarcomere length [1]. Higher force beyond 4mm is expected to increase the hysteresis of titin by increasing Ig domain unfolding. Rabbit psoas myofibrils were used for these experiments. Single myofibrils with an initial mean sarcomere length (SL) of 2.8mm were activated with Caþ2 and ATP (no Caþ2 for passive) and lengthened to approximately 4.5mm and then immediately cycled (10x) 50.25mm. Mean 1 peak force was higher in active (n1⁄46) versus passive (n1⁄45) at 338.95137.2nN/mm versus 103.2517.2nN/mm, as expected. Mean peak force fell continuously from the 1 to the 10 cycle in active, while the peak force stabilized in passive tests by the 4 cycle. Hysteresis was greater in the active tests; mean 1 cycle hysteresis was 10.855.4nN$mm versus 1.350.9nN$mm. We conclude that the higher forces observed at all SL for active compared to passive lengthening results in increased visco-elastic behaviour in titin through increased Ig domain unfolding and this unfolding is not completed in active tests even after 10 repeated stretch-shortening cycles at long SL. [1] Leonard and Herzog, 2010, AJP-(Cell) 299:14-20.