Muscle contraction: A new interpretation of the transient behaviour of muscle

Abstract

Piazzesi et al. [G. Piazzesi, L. Lucii, V. Lombardi, J. Physiol. 545 (2002) 145–151] made a study on the muscle transients due to step changes in force using improved time resolution and recorded filament movement and shortening velocities in the four phases. They point to Phase 2 and to Phase 4 (working muscle) and claim that their results do not contradict the swinging-cross-bridge (SCB) model which has a much-quoted constant power stroke of about 150 Å (their value of 70 Å was smaller). Siding with the SCB model, they nevertheless record that the power stroke decreases with load. We are pleased with this experimental result as it conforms to our theory, published in 1996, of an impulsive model with a much smaller step-size distance z (≈20 Å). Using their data we obtain precise interval times and estimates of filament movement in Phase 2 and in working muscle. Our first result is that the time frames (interval times) for Phase 2 are the same as in working muscle. Moreover, we demonstrate that the authors’ data verify the correctness of our calculated z values. There are eight active ATP events in Phase 2 in time frame t compared to one in working muscle in the same time frame t. This gives, for the first time, precise numbers for contractile events. We show that the SCB model is incorrect and our analysis supports the impulsive model with a much smaller filament (zero-load) motion, ≈20 Å per ATP split.

Introduction

The basic question in muscle research is how much movement between the actin and myosin filaments occurs per ATP split. There are two models to consider: the cross-bridge model pioneered by Huxley in 1957 [1] and the impulsive model described by us in a series of papers [2], [3], [4], [5].

These ideas have been presented in detail by us previously [5] but there is still a need to reexamine the correctness of our ideas. Accordingly, we will briefly summarize the present situation. We refer to the movement between filaments per ATP split as the step-size distance z, whereas in the cross-bridge model it is referred to as the working-stroke or the power-stroke h. The cross-bridge model [1] has a power-stroke of h ≈ 150 Å. The evidence for the 150 Å power-stroke in the cross-bridge model is based upon the analysis of the transients due to length step changes by Ford et al. in 1977 [6]. In the impulsive model, z is much smaller, the order of 20 Å for five sets of different data [5]. This smaller value for z is obtained from the step-size distance equation and the energy rate equations coupled with the enthalpy available per ATP split [2].

Now transient experiments are of two sorts as described by Woledge et al. [7] involving step changes in force, e.g. Podolsky [8] or the much studied step changes in length, e.g. Ford et al. [6].

But in the mid-1990s, a complication to the transient studies arose as it was found that ≈ 50% of the compliance within the sarcomere resides in the filaments themselves (compliance is the reciprocal of stiffness). Attention was later returned to the transient experiments involving step changes in force. In this case the velocity and length transients following a force step are free from this complication, Piazzesi et al. [9]. These authors have reported a new study on these transients using an improved time resolution of 1 μs, the experiments are a significant advance on previous work. The title of this paper is “the size and speed of the working stroke of muscle myosin and its dependence on the force” [9]. By size they refer to the filament movement, which is the working stroke and by speed they refer to the shortening velocity measurement. The authors concluded that their results support the 150 Å working stroke of the cross-bridge model [9]. It would, therefore, appear that this new data might be crucial in deciding the correctness of the two models. However, we believe there is a straightforward interpretation of the force-step data, which fully supports the correctness of the impulsive model and consequently contradicts the 150 Å working stroke of the cross-bridge model.

Before describing our new interpretation of the transient behaviour of muscle we first need to describe the new experimental results.