Cross-Bridge Populations and the Biphasic Time Course of Muscle Relaxation

Abstract

A biphasic time course of relaxation follows Ca2+ removal from a contracting muscle fiber--a small linear decline is followed by a faster large exponential drop in tension to the relaxed state. Our aim is to see if recent insights into tension generation and the cross-bridge cycle can shed light on these kinetics (Davis and Epstein, 2009). In fully activated isometric rabbit psoas fibers two distinct and roughly equal populations of myosin heads are attached to actin. Half are termed “competent” and are capable of generating tension, while the other half are termed “noncompetent” and serve to “buffer” tension. For example, a step-decrease in fiber length releases a steric constraint on noncompetent cross-bridges thereby triggering tension recovery. We investigate whether the “buffer” of noncompetent AMD bridges might support the linear phase, with the exponential decline (kREL FAST) mediated by the decay of the remaining competent cross-bridge population. To do this, the linear phase was treated as a steady-state reaction with duration and not slope used to determine kREL SS. We found kREL SS normalized to kCAT (fiber ATPase) if a reasonable ∼21% of myosin heads constitute the noncompetent buffer. This leaves the final exponential decline to the relaxed state governed by the discharge of tension generating competent cross-bridges on exhaustion of the noncompetent buffer population. Additional support comes from the observations that added Pi decreases the duration and increases the slope of the linear phase with virtually no effect on kREL FAST (Tesi et al, 2002), and that a slow Tn Ca2+ off switch prolongs the linear phase (Kreutziger et al, 2008). Arrhenius plots of kCAT, kREL SS and kREL FAST are similar in slope, suggesting a common rate-limiting step of strain-sensitive ADP cross-bridge dissociation for all processes.