Mechanism of tension generation in muscle: an analysis of the forward and reverse rate constants.
Tension generation in muscle occurs during the attached phase of the ATP-powered cyclic interaction of myosin heads with thin filaments. The transient nature of tension-generating intermediates and the complexity of the mechanochemical cross-bridge cycle have impeded a quantitative description of tension generation. Recent experiments performed under special conditions yielded a sigmoidal dependence of fiber tension on temperature--a unique case that simplifies the system to a two-state transition. We have applied this two-state analysis to kinetic data obtained from biexponential laser temperature-jump tension transients. Here we present the forward and reverse rate constants for de novo tension generation derived from analysis of the kinetics of the fast laser temperature-jump phase tau(2) (equivalent of the length-jump phase 2(slow)). The slow phase tau(3) is temperature-independent indicating coupling to rather than a direct role in, de novo tension generation. Increasing temperature accelerates the forward, and slows the reverse, rate constant for the creation of the tension-generating state. Arrhenius behavior of the forward and anti-Arrhenius behavior of the reverse rate constant is a kinetic signature of multistate multipathway protein-folding reactions. We conclude that locally unfolded tertiary and/or secondary structure of the actomyosin cross-bridge mediates the power stroke.
Davis
Julien S
JS
Molecular Physiology Section, Laboratory of Molecular Cardiology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. davisjs@nhlbi.nih.gov
Epstein
Neal D
ND
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003198:Computer Simulation; D007537:Isometric Contraction / Q000502:physiology*; D007700:Kinetics; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000502:physiology*; D011817:Rabbits; D013314:Stress, Mechanical; D013696:Temperature
D000255:Adenosine Triphosphate