Phosphorylation thin filament regulation

The second aspect of the force-RLC phosphorylation relation that suggests additional regulation is illustrated by alterations in the slope of the relation (Fig. 1, lower right). Alterations in isometric force at fixed values of RLC phosphorylation are probably the strongest evidence for the in vivo operation of thin filament regulation. Smooth muscle contains two thin filament proteins, caldesmon and calponin, that inhibit actin-activated MgATPase activity of phosphorylated myosin. This inhibitory activity is reversed by the binding of Ca +ZCaM or by phosphorylation, and thus CD and CP may modulate the RLC phosphorylation... 

The sufficiency of myosin phosphorylation for contraction in smooth muscle is indisputably demonstrated in experiments where the addition of pro-teolyzed CaM-independent MLCK to permeabilized fibers brings about contraction at very low [Ca +] (Walsh et al, 1982). Furthermore, injection of CaM-independent MLCK into single smooth muscle cells results in contraction under conditions where [Ca +]j remains at resting values (Itoh et al, 1989). These results tend to rule out a model in which thin filaments are fully inhibited in resting muscle, and require Ca2+-dependent disinhibition to support contraction. However, these experiments do not rule out the possibility that thin filament-binding proteins modulate the contractile response. Alterations in the RLC phosphorylation-force relation in intact muscle indicate that collateral regulation can occur. Moreover, experiments with permeabilized fibers demonstrate that thin filament-binding proteins can inhibit force independent of RLC phosphorylation (Pfitzer et al,... 

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