The myosin converter region influences cross‐bridge stiffness and muscle kinetics

The converter has been proposed to be the myosin elastic element that sets cross‐bridge stiffness. According to most cross‐bridge models, the elastic element's stiffness should directly influence muscle fiber type force and power generation levels. We tested these hypotheses by using the natural variation in converter regions found in Drosophila muscle types. In Drosophila , myosin isoforms are generated by alternative splicing from a single myosin heavy chain gene. The converter region is encoded by five alternative exon versions. We expressed four non‐native versions in Drosophila indirect flight muscle (IFM) and found that two of the three versions, 11b and 11e (found in larval and adult body wall muscles) decreased IFM rigor stiffness by 63% and 43%, respectively. This supports the hypothesis that the converter is the critical elastic element of myosin. The converters also influenced IFM fiber and myosin kinetics. 11b, 11d, and 11e decreased the frequency at which maximum power was generated (f max ) by 28%, 40%, and 53%, respectively. All three decreased myosin attachment kinetics, however, 11d and 11e also increased detachment kinetics. Differences in force generation are minimal, likely due to myosin stiffness changes being offset by changes in myosin duty ratio. With little to no force differences, changes in muscle power almost directly correlated with f max . All three lines displayed reduced wing beat frequency, 11 to 15% less than control lines, with flight performance better correlating with fiber f max than cross‐bridge stiffness. Thus, the converter is critical for muscle fiber type diversity as it helps set myosin stiffness, cross‐bridge kinetics and muscle power generation. Supported by NIH grant R01 AR055611 to D.S.