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Effects of modulators of myosin phosphorylation on isometric force and shortening velocity in skinned smooth muscle.

Using different modulators of myosin phosphorylation, we were able to demonstrate several different relations between Fo and Vus. The data from our studies using phosphatase indicate that force and velocity may be similarly influenced by high concentration of this enzyme which is known to modulate phosphorylation. H8, however, generated a relation in which Vus is sensitive to this modulator of myosin phosphorylation and Po is relatively insensitive except at high concentrations of H8. Whether these relations are attributable to changes in phosphorylation is still questionable and under investigation. Because H8 is competitive with respect to ATP and the effect is calcium-insensitive, it may instead have a direct effect on the actin-myosin interaction. ML9, a compound which has been reported to have effects upon MLCK through a mechanism similar to that of H8, yields a relation different than H8 but similar to the phosphatase, that is, both force and velocity decreased in a nearly parallel manner. Using these modulators, we have found that the relation between Po and Vus is not unique, reinforcing the hypothesis that crossbridge number and cycle rate may be independently modulated in smooth muscle. (Paul, 1989).