DmeEX0005112 @ dm6

Replacing the endogenous converter with an embryonic version decreased SA tension and the rate of SA tension generation. The alterations in SA properties and myosin kinetics from the converter exchange caused power generation to drop to 10% of control fiber power when the optimal conditions for control fibers - 1% muscle length (ML) amplitude and 150 Hz oscillation frequency - were applied to fibers expressing the embryonic converter (IFI-EC). Optimizing conditions for IFI-EC fiber power production, by doubling ML amplitude and decreasing oscillation frequency by 60%, improved power output to 60% of optimized control fiber power. IFI-EC flies altered their aerodynamic flight characteristics to better match optimal fiber power generation conditions as wing beat frequency decreased and wing stroke amplitude increased. This enabled flight in spite of the drastic changes to fiber mechanical performance. IFI isoform: DmeEX0005112; EMB: DmeEX0005115

The authors studied the influence of the converter, a myosin structural region at the junction of the lever arm and catalytic domain, using Drosophila because its single myosin heavy chain gene expresses five alternative converter versions (11a-e; DmeEX0005112-6). the authors created five transgenic fly lines, each forced to express one of the converter versions in their indirect flight muscle (IFM) fibers. Electron microscopy showed that the converter exchanges did not alter muscle ultrastructure. The four lines expressing converter versions (11b-e) other than the native IFM 11a converter displayed decreased flight ability. IFM fibers expressing converters normally found in the adult stage muscles generated up to 2.8-fold more power and displayed up to 2.2-fold faster muscle kinetics than fibers with converters found in the embryonic and larval stage muscles. Small changes to stretch-activated force generation only played a minor role in altering power output of IFM. Muscle apparent rate constants, derived from sinusoidal analysis of the chimeric converter fibers, showed a strong positive correlation between optimal muscle oscillation frequency and myosin attachment kinetics to actin, and an inverse correlation with detachment related cross-bridge kinetics. This suggests the myosin converter alters at least two rate constants of the cross-bridge cycle with changes to attachment and power stroke related kinetics having the most influence on setting muscle oscillatory power kinetics.

The authors measured FVR properties of Drosophila jump muscle fibers from five transgenic lines each expressing a single converter. Consistent with the hypothesis, the authors observed up to 2.4-fold alterations in FVR curvature. Maximum shortening velocity (v0) and optimal velocity for maximum power generation were also altered, but isometric tension and maximum power generation were unaltered. Converter 11a, normally found in the indirect flight muscle (IFM), imparted the highest FVR curvature and v0, whereas converter 11d, found in larval body wall muscle, imparted the most linear FVR and slowest v0. Jump distance strongly correlated with increasing FVR curvature and v0, meaning flies expressing the converter from the IFM jumped farther than flies expressing the native jump muscle converter. Fitting the data with Huxley's two-state model and a biophysically based four-state model suggest a testable hypothesis that the converter sets muscle type FVR curvature by influencing the detachment rate of negatively strained myosin via changes in the force dependence of product release.