Molecular and Physiological Mechanisms of Muscle Contraction PDF

PREFACE

Frog and rabbit are the principal animal species studied in this monograph. The passage from one species to another may make it difficult to follow the reasoning, but this passage is necessary because most of the experimental results concerning physiological properties (e.g. isometric tetanic tension and velocity of shortening) were obtained with intact frog fibres, whereas most of the enzymatic results concerning MgATPase activities were obtained with demembranated rabbit fibres.

This book comprises a long line of reasoning, with many interdependent and complex sections. I therefore recommend reading the titles of the most complicated chapters and sections carefully to facilitate understanding. Consulting the Index could also be useful.

In addition to reviewing and reanalysing the results of studies of my own and many other independent groups, I also report unpublished results for experiments with half-fibres (intact fibres split lengthwise) from white skeletal muscles of young adult frogs and with permeabilised fibre bundles from red skeletal muscles of young adult rats. From this many-faceted ‘treatise’, a hybrid model emerges, combining the swinging crossbridge/ lever-arm processes and lateral swelling mechanisms.

In these new experimental findings, the relative resting force, recorded at pH 7 and 10°C, in half-fibres from white skeletal muscles (iliofibularis) of young adult frogs (Rana pipiens), held around the slack length, increased very slightly when the bulk ionic strength was lowered from 180 mM to ~40 mM. Between ~40 mM and ~30 mM, the relative resting force increased very rapidly with further decreases in ionic strength, peaking at high levels, between ~30 mM and ~20 mM. Below ~20 mM, the relative resting force decreased sharply. The dependence of the relative resting force on ionic strength, the existence of a maximum and the rapid decrease at very low ionic strengths demonstrate that strong radial repulsive electrostatic forces are exerted between the myofilaments under resting conditions (see below concerning the conversion of radial forces into axial forces). These radial repulsive electrostatic forces are also effective in half-fibres (and all types of fibre, whether intact or demembranated), under isometric tetanic contraction conditions, and present qualitative characteristics similar to those at rest (only some quantitative features differ).

In another set of experiments, myosin heads were cleaved enzymatically (i.e. digested with α-chymotrypsin) from the rest of the thick myosin filaments, in permeabilised fibre bundles from red skeletal muscles (tibialis anterior) of young adult rats (Wistar), held around the slack length, in a buffer mimicking the physiological resting medium, at room temperature. Very small, sometimes tiny, but detectable, transitory contractures resulted from these enzymatic cleavages, demonstrating that thin actin and thick myosin filaments are  tethered by a small number of ‘resting’ (weakly bound) cross-bridges, exerting strong radial tethering forces (together with weak radial attractive/ compressive forces) that counterbalance the radial repulsive electrostatic forces, under resting conditions