Thermogenic regulation of the simple harmonic motion of tropomyosin byweak-binding myosin cross-bridges explains spontaneous oscillatory contractions.

Abstract

A sarcomeric regulatory role for weak-binding, disordered cross-bridges (dXbs) of the myosin disordered-relaxed state is described which explains spontaneous oscillatory contractions (SPOCs). The simple harmonic (SH) theory proposes that as tropomyosin (Tm) interacts with thin filament the random vibrational motion begins to vibrate harmonically with the actin repeat interval (i.e., simple harmonic motion, SHM). This interaction increases as the thick filament electrostatic force increases as lattice spacing decreases by stretch or osmotic compression, causing the SHM to increase with displacement of Tm from thin filament OFF to ON position, exposing sites for cross-bridge formation and force generation. Troponin inhibits this process with decreasing calcium. A thermogenic mechanism is implicit in the SH theory whereby the random/Brownian motion of molecules that interact with Tm modulate the random motion of Tm which, in turn, is regulated harmonically. Heat and internal work from external sources and hydrolysis of ATP are primary sources for Brownian motion of sarcomeric molecules including dXbs which are likely a major source for modulating the SHM thermogenicly. Initially, at partial activation, by calcium or ADP, the increase in dXbs causes thermogenic vibrational energy and SHM of Tm to increase. Thermogenic activation continues throughout the slow contraction phase of SPOCs. Subsequent rapid elongation/relaxation phase occurs as the thermogenic process reaches its limit, as 1) dXbs decrease as force generating cross-bridges increase, 2) contractile efficiency increases (i.e., less heat/internal work) as shortening velocity decreases, and 3) thermogenic excitation by dXbs decreases as lattice spacing increases. The inhibitory force of troponin now overcomes the SHM of Tm which rapidly returns to initial partial OFF/ON conditions and the cycle repeats. Propagation of SPOC waves and implications for the regulatory mechanism of MyBP-C are discussed.