Proceedings of The Physiological Society

University College Dublin (2009) Proc Physiol Soc 15, C37

Oral Communications

How many myosin heads act on a single actin filament at any instant in working muscle?

G. F. Elliott1, C. R. Worthington2

1. Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, United Kingdom. 2. Physics and Biology, Carnegie-Mellon University, Pittsburgh, Pennsylvania, USA.

If N is the number of myosin heads acting on a single actin filament in vertebrate striated muscle, working at any instant to produce tension, stoichiometry gives 150 ≥ N ≥ 1; the actual value of N is clearly an important parameter. Stiffness measurements have long been used to estimate N, though a warning was sounded [1] after X-ray measurements showed that a sizeable amount of the muscle compliance arose from the actin and myosin filaments. The usual approach compares the instantaneous stiffness measured during quick stretch or quick release in rigor and contraction. Immediately after this response, though, the time scales of the tension response are very different: in rigor the tension persists for several tens of ms; in contraction it changes with a half time of a few ms. This stiffness approach makes three inherent assumptions: (i) in rigor N = 150 (here resisting extension rather than producing tension); (ii) the rigor stiffness is the same as when the interactions are producing tension; (iii) the filament compliance is the same in contraction as in rigor. However Kawai and Brandt showed that the stiffness of rigor (crayfish) single fibres could change by a factor of two or more depending on the approach to rigor [2]. Therefore the assumptions are probably over-optimistic, especially given the differences in ionic composition of the solutions used to induce the various states. For all these reasons we think it wise to accept the warning of Goldman and Huxley [1], that ‘stiffness cannot be used safely as a measure of cross-bridge attachment’, and we choose to discount numbers derived from stiffness measurements. It is a pity that there is no independent experimental method to estimate N. We present a model (derived from other physiological and biochemical data) where the average time between impulses on an actin filament is one or two ms and that gives an inherent natural explanation of AV Hill’s force-velocity equation from first principles [3]. The model gives physical meaning to Hill's constants 'a' and 'b' and it also implies that the size of the individual contractile impulse in situ between an actin filament and one myosin head must be approximately 140 (an impulse has the dimensions of force x time). The impulses normally act sequentially in time along the filament [4]. In response to a fast perturbation, however, extra impulses may occur within the same time frame [5]. Our impulse model provides an alternative estimate of N; accumulating biochemical evidence supports our view that N is of the order of 1 in normal contraction and 8-9 in transient recovery after quick release.

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