Cooperativity in the Ca²⁺-Regulation of Skeletal Muscle Contraction

Abstract

An increase in intracellular Ca2⁺ initiates muscle contraction for all types of muscle. In striated muscles the Ca²⁺ binds to the muscle thin filaments and relieves the inhibition of myosin binding to actin allowing the ATP driven actomyosin cross bridge cycle which results in contraction. Although we know all of the essential components and the signal transduction pathway which leads from the change in free Ca²⁺ concentration to the contraction of a muscle fiber, the molecular details of the turning-on process are poorly understood. The change in Ca²⁺ concentration does not simply turn the contraction on and off but the exact concentration and the rate of change of concentration produces a graded response in the cross bridge cycle. The system is complex and involves at least 6 distinct protein subunits assembled into µm long filaments that are themselves assembled into a precise 3-dimensional array of interdigitating filaments. Each subunit interacts with more than one partner in a series of steric and allosteric interactions which may propagate along the thin filament. The potential for long range cooperative interactions involving hundreds or thousands of molecules is clearly present and part of the object of this chapter is to define the extent to which such long range interactions occur. The level of cooperativity is illustrated in Fig. 1, which shows the Ca²⁺ dependence of the force developed by an isometrically contracting skinned muscle fiber.