Simple harmonic motion of tropomyosin: proposed mechanism for length-dependent regulation of muscle active tension

Abstract

A simple harmonic theory is proposed to describe the regulatory mechanism of tropomyosin in the activation of muscle contraction. The theory proposes that activation-associated displacement of tropomyosin is inherent to tropomyosin, a consequence of the molecule's large-scale vibrational motion (5-10 A root mean square displacement). In association with thin filament the vibrational motion may become less complex, approaching the ideal case of simple harmonic motion. The degree of activation increases as the amplitude of the simple harmonic motion increases, causing tropomyosin to shorten lengthwise, shiftings its position from the periphery of thin filament (OFF) to the actin groove (ON). The amplitude may be regulated in a rectilinear manner by the thick filament electrostatic force, the thin filament hydrophobic force, and the Ca(2+)-dependent force of the troponin complex. The radial and tangenital components of the resultant force may vary as the muscle is stretched, regulating maximum active tension and Ca2+ sensitivity, respectively. This may represent the molecular basis for Starling's law of the heart. The mechanism may be important for describing the regulatory mechanism of tropomyosin in smooth muscle and nonmuscle cells and may facilitate a clinically relevant understanding of the effects of pH, Mg2+ concentration, ionic strength, and ethanol on the regulation of active tension.