The load dependence of muscle's force-velocity curve is modulated by alternative myosin converter domains.

Abstract

The hyperbolic shape of the muscle force-velocity relationship (FVR) is characteristic of all muscle fiber types. The degree of curvature of the hyperbola varies between muscle fiber types and is thought to be set by force-dependent properties of different myosin isoforms. However, the structural elements in myosin and the mechanism that determines force dependence are unresolved. We tested our hypothesis that the myosin converter domain plays a critical role in the force-velocity relationship (FVR) mechanism. Drosophila contains a single myosin heavy chain gene with five converters encoded by alternative exons. We measured FVR properties of Drosophila jump muscle fibers from five transgenic lines each expressing a single converter. Consistent with our hypothesis, we 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 our 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.