Myosin Heavy Chain Isoforms Influence the Magnitude of Stretch Activation in Drosophila Muscles

Abstract

The stretch activation (SA) mechanism, a general property of all muscle types, is most prominent in muscles that generate power through cyclical contractions, such as insect indirect flight muscles (IFM) and vertebrate cardiac muscles. SA is defined as phase 3, a delayed tension increase, of the tension transient following a muscle stretch. We are testing our hypothesis that myosin heavy chain isoforms help set SA magnitude and hence power generating ability in different muscle types. The Drosophila thorax contains two muscle types, IFMs and jump muscles. In IFMs, the magnitude of SA is great enough to enable net positive power generation when it is fully calcium activated. In contrast, jump muscles display very little stretch activation and cannot generate net positive power when fully activated. We found that when an embryonic myosin isoform (EMB) is transgenically expressed in the jump muscle, the muscle is transformed and behaves like a moderately stretch-activatable muscle. The transformed muscle can now generate positive power and SA magnitude is increased by ∼60% at 0mM Pi and ∼350% at 16mM Pi. This shows that SA magnitude is influenced by myosin isoforms. We found that power generation is [Pi] dependent as ≥ 2mM Pi is required for power production in jump muscles expressing the EMB isoform. Expressing the IFM isoform in jump muscles did not enable positive power generation or increase SA magnitude. To further test our hypothesis, we are expressing the jump myosin isoform in IFMs to determine if this reduces IFM SA magnitude. We conclude that myosin isoforms can influence the magnitude of SA, but are not the only mechanism responsible for natural differences in SA magnitude.