Decomposition of activation process of skeletal muscle : potent acceleration of the rate-limiting step of contracting reaction by exogenously added active actin

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Within the activation process of skeletal muscle decomposed into two steps : 1) the initiation of activation process induced by calcium-binding to regulatory proteins, and 2) the following self-regenerative activation process in which active contractile myosin heads recruit adjacent inactive myosin heads to contractile interaction with actin, it is likely that muscle fatigue hinders the latter self-regenerative process to reduce the maximal force and shortening velocity. Therefore, in the present study, we focused on the effect of the tension on the latter step using phosphate analog.The broad ^<19>F-NMR spectrum of the phosphate analog (AlFx) bound to myosin heads indicated that the analogs hardly exchange with the free AlFx in solution and the analog-bound myosin has little mobility in the sarcomeres. The X-ray diffraction pattern also indicated that the analog-bound myosin heads kept helically ordered arrangement around the thick filament backbone even at low temperature. The time c … More ourse of the analog release estimated from the recovery of initial rapid tension development of the fiber was the same as the change of the diffraction pattern suggesting that the rate-limiting step of the analog release is binding step of myosin to actin.The exogenous actin fragment activated the analog release significantly as expected, however, stretch activation was not observed for the acceleration exerted by exogenous actin fragment. Since exogenous actin fragment is free from sarcomere structure and does not bear strain generated by contractile myosin heads, the strain on thin filaments is considered to be necessary to enhance the self-regenerative activation process by stretch.Any of so far proposed mechanisms of muscle fatigue could not suppress contractility of skeletal muscle adequately. We consider that the self-regenerative process activated by actin binding with modulation through strain in thin filament synergistically amplifies the integrated suppressing effect beyond a simple summation. Less