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Modulators of actin-myosin dissociation: basis for muscle type functional differences during fatigue

Karatzaferi, Christina, Adamek, Nancy, Geeves, Michael A. (2017) Modulators of actin-myosin dissociation: basis for muscle type functional differences during fatigue. American Journal of Physiology - Cell Physiology, 313 (6). C644-C654. ISSN 0363-6143. E-ISSN 1522-1563. (doi:10.1152/ajpcell.00023.2017) (KAR id:64123)

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The muscle types present with variable fatigue tolerance, in part due to the myosin isoform expressed. However, the critical steps that define 'fatigability' in vivo of fast vs slow myosin isoforms, at the molecular level, are not yet fully understood. We examined the modulation of the ATP-induced myosin sub-fragment 1 (S1) dissociation from pyrene-actin by inorganic phosphate (Pi), pH and temperature using a specially modified stopped-flow system that allowed fast kinetics measurements at physiological temperature. We contrasted the properties of rabbit psoas (fast) and bovine masseter (slow) myosins (obtained from samples collected from New Zealand rabbits and from a licensed abattoir, respectively, according to institutional and national ethics permits). To identify ATP cycling biochemical intermediates, we assessed ATP binding to a pre-equilibrated mixture of actomyosin and variable [ADP], pH (pH 7 vs pH 6.2) and Pi (zero, 15 or 30 added mM Pi) in a range of temperatures (5 to 45°C). Temperature and pH variations had little, if any, effect on the ADP dissociation constant (KADP) for fast S1 but for slow S1 KADP was weakened with increasing temperature or low pH. In the absence of ADP, the dissociation constant for phosphate (KPi) was weakened with increasing temperature for fast S1. In the presence of ADP, myosin type differences were revealed at the apparent phosphate affinity, depending on pH and temperature. Overall, the newly revealed kinetic differences between myosin types could help explain the in vivo observed muscle type functional differences at rest and during fatigue.

Item Type: Article
DOI/Identification number: 10.1152/ajpcell.00023.2017
Uncontrolled keywords: myosin kinetics, cross-bridge cycle, temperature, muscle fatigue
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > School of Biosciences
Depositing User: Michael Geeves
Date Deposited: 23 Oct 2017 10:47 UTC
Last Modified: 29 May 2019 19:44 UTC
Resource URI: (The current URI for this page, for reference purposes)
Geeves, Michael A.:
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