A theory on auto-oscillation and contraction in striated muscle

It is widely accepted that muscle cells take either force-generating or relaxing state in an all-or-none fashion through the so-called excitation–contraction coupling. On the other hand, the membrane-less contractile apparatus takes the third state, i.e., the auto-oscillation (SPOC) state, at the activation level that is intermediate between full activation and relaxation. Here, to explain the dynamics of all three states of muscle, we construct a novel theoretical model based on the balance of forces not only parallel but also perpendicular to the long axis of myofibrils, taking into account the experimental fact that the spacing of myofilament lattice changes with sarcomere length and upon contraction. This theory presents a phase diagram composed of several states of the contractile apparatus and explains the dynamic behavior of SPOC, e.g., periodical changes in sarcomere length with the saw-tooth waveform. The appropriate selection of the constant of the molecular friction due to the cross-bridge formation can explain the difference in the SPOC periods observed under various activating conditions and in different muscle types, i.e., skeletal and cardiac. The theory also predicts the existence of a weak oscillation state at the boundary between SPOC and relaxation regions in the phase diagram. Thus, the present theory comprehensively explains the characteristics of auto-oscillation and contraction in the contractile system of striated muscle.     

Regulation of vertebrate striated muscle contraction

Most current textbooks of cell biology and histology use the steric blocking model to describe the protein mechanism by which vertebrate striated muscle contraction is regulated. Evidence accumulated in the past decade, however, reveals the regulation of muscle contraction to be far more complex than this model predicts.     

Calcium-dependent muscle contraction in obliquely striated Ascaris suum muscle

The regulatory proteins of Ascaris suum striated skeletal muscle were partially purified and characterized. A tropomyosin isoform (Mr 41K) and three troponin subunits identified as troponin T (Mr 37.5K), troponin I (Mr 25.5K) and troponin C (Mr 18.5K) were purified. Three myosin light chains (Mr 25K, 19K, and 17K) were isolated from washed Ascaris actomyosin; the 19K subunit was phosphorylated in vitro. A calcium/calmodulin-dependent myosin light chain kinase activity was identified in the muscle. In contrast to previously reported data suggesting that Ascaris obliquely striated muscle contraction is regulated by a myosin-mediated mechanism, these data indicate that all of the proteins required for actin-mediated, calcium-dependent muscle contraction are present in this tissue.     

A new hybrid theory of muscle contraction

This work represents an attempt to find a more complete and adequate interpretation of the phenomenon of muscle contraction than is presently available. Arguments are presented in favour of the idea that the principal groups of existing theories on contraction contain both elements that should be excluded from consideration and elements that are of particular interest to retain. In the present theory, it is accepted that the essential process in muscle contraction is a relative increase in long-range repulsive forces, exerted directly perpendicular to the myofilaments. It is then assumed that these forces of repulsion are converted into forces which shorten the fibre, by way of a passive mechanical action of obliquely arranged cross bridges between the thick and thin filaments. Analysis of important experimental data serves to emphasize the explicative potential of the new theory.     

A simple kinetic model of contraction of striated muscle: Full activation at full filament overlap in sarcomeres

A simple kinetic model of muscle contraction is suggested. The rates of cross-bridge transitions from one kinetic state to another one are supposed to depend on the strain averaged over an ensemble of actin-bound bridges. With a proper set of strain-dependent rate constants, the model fits well a broad range of experimental data. Owing to that the strain-stress relation is described by a set of ordinary differential equations, the model can be used for simulating complex 3D muscle contractions.     

A dynamic model of smooth muscle contraction

A dynamic model of smooth muscle contraction is presented and is compared with the mechanical properties of vascular smooth muscle in the rat portal vein. The model is based on the sliding filament theory and the assumption that force is produced by cross-bridges extending from the myosin to the actin filaments. Thus, the fundamental aspects of the model are also potentially applicable to skeletal muscle. The main concept of the model is that the transfer of energy via the cross-bridges can be described as a 'friction clutch' mechanism. It is shown that a mathematical formulation of this concept gives rise to a model that agrees well with experimental observations on smooth muscle mechanics under isotonic as well as isometric conditions. It is noted that the model, without any ad hoc assumptions, displays a nonhyperbolic force-velocity relationship in its high-force portion and that it is able to maintain isometric force in conditions of reduced maximum contraction velocity. Both these findings are consistent with new experimental observations on smooth muscle mechanics cannot be accounted for by the classical Hill model.     

Kinetic model of a single muscle contraction

A model of single muscle contraction is proposed. The kinetics of two reactions have been used: interaction between the excitation mediator and the muscle membrane receptor, and the reaction of enzymatic mediator splitting. The muscle contraction parameters have been correlated with the concentration of the mediator-receptor complex.     

On a simple way to verify the experimental agreement of any two-state mathematical model of muscle contraction

In the usual theories of muscular contraction, the crossbridges are considered to be the force generators leading to the sliding of the thick and the thin filaments past each other. The first mathematical treatment of such models was that of Huxley (1957) and since this date the formalism has been continuously improved. Here we have obtained a relation identifiable to the mathematical expression of the Fenn effect. This relation leads to a new expression of the tension P(V), which must be compared with that directly obtained from mechanical considerations. These two expressions do not fit in the currently accepted two-state models.     

Calcium efflux during the cold-induced contraction of mammalian striated muscle fibres

The efflux of ⁴⁵Ca from mammalian slow twitch muscle fibres has been studied to provide a measure of the concentration of free Ca²⁺ in the sarcoplasm. The kinetically complex early phases of washout of the isotope are succeeded by a prolonged slower phase which exhibits first-order kinetics. This later phase is accelerated by caffeine, by preventing oxidative phosphorylation and also during an isometric contraction, whether this contraction is produced by lowering the temperature or by electrical stimulation. The local anaesthetic tetracaine abolishes the contraction caused by cold and in this case the rate constant for efflux is progressively lowered as the temperature is reduced (Q₁₀ value of 2.3). The removal of external Na⁺ and Ca²⁺ reduces the efflux rate constant. Caffeine, sodium removal and the inhibition of oxidative phosphorylation, all potentiate the cold contraction and the associated extra ⁴⁵Ca efflux. Ca removal causes the cold contraction to become phasic. It appears that caffeine, sodium removal, the inhibition of oxidative phosphorylation and a decrease in temperature to below 10°C are all treatments which, like electrical stimulation, increase the sarcoplasmic free calcium concentration to varying degrees.