Key result
In intact airway smooth muscle, activation increased thick filament density by 144%, while the absence of calcium decreased filament density by 35% in relaxed muscle.
In airway smooth muscle, filamentous myosins exist in equilibrium with monomeric myosins, with muscle activation favoring filament formation and resting calcium levels being crucial for preservation of filaments in the relaxed state.
Hypothesis-generating for myosin filament dynamics in airway disease; leaves open therapeutic targeting pending human validation.
Myosin thick filaments have been shown to be structurally labile in intact smooth muscles. Although the mechanism of thick filament assembly/disassembly for purified myosins in solution has been well described, regulation of thick filament formation in intact muscle is still poorly understood. The present study investigates the effect of resting calcium level on thick filament maintenance in intact airway smooth muscle and on thick filament formation during activation. Cross-sectional density of the thick filaments measured electron microscopically showed that the density increased substantially (144%) when the muscle was activated. The abundance of filamentous myosins in relaxed muscle was calcium sensitive; in the absence of calcium (with EGTA), the filament density deceased by 35%. Length oscillation imposed on the muscle under zero-calcium conditions produced no further reduction in the density. Isometric force and filament density recovered fully after reincubation of the muscle in normal physiological saline. The results suggest that in airway smooth muscle, filamentous myosins exist in equilibrium with monomeric myosins; muscle activation favors filament formation, and the resting calcium level is crucial for preservation of the filaments in the relaxed state.
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Herrera et al. (2002) studied this question. Calcium level and muscle activation vs. Absence of calcium (with EGTA) / relaxed state was evaluated on Cross-sectional density of thick filaments. In intact airway smooth muscle, activation increased thick filament density by 144%, while the absence of calcium decreased filament density by 35% in relaxed muscle.
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