An Embryonic Myosin Isoform Enables Stretch Activation and Cyclical Power in Drosophila Jump Muscle

Zhao, Chuanzhi; Swank, Douglas M.

doi:10.1016/j.bpj.2013.04.057

Cited by 9 publications

(21 citation statements)

References 53 publications

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“…Such a strain-dependent detachment could involve reversal of the myosin power stroke, which has been observed and modeled to be sensitive to Pi availability ( Dantzig et al, 1992 ; Smith and Geeves, 1995 ), or possibly without reversal but still sensitive to Pi ( Debold et al, 2013 ). Other observations consistent with either mechanism include a Pi-enhanced rate of tension development after rapid temperature change ( Ranatunga, 1999 ), a significantly shorter myosin crossbridge lifetime observed in the laser trap assay when Pi is abundant ( Baker et al, 2002 ), a reduced rate of free Pi generation in activated striated muscle undergoing stretch ( Mansfield et al, 2012 ), and an enhanced oscillatory work and power with increasing Pi ( Zhao and Swank, 2013 ).…”

Section: Discussionmentioning

confidence: 94%

Enhancing diastolic function by strain-dependent detachment of cardiac myosin crossbridges

Palmer

Swank

Miller

et al. 2020

Journal of General Physiology

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The force response of cardiac muscle undergoing a quick stretch is conventionally interpreted to represent stretching of attached myosin crossbridges (phase 1) and detachment of these stretched crossbridges at an exponential rate (phase 2), followed by crossbridges reattaching in increased numbers due to an enhanced activation of the thin filament (phases 3 and 4). We propose that, at least in mammalian cardiac muscle, phase 2 instead represents an enhanced detachment rate of myosin crossbridges due to stretch, phase 3 represents the reattachment of those same crossbridges, and phase 4 is a passive-like viscoelastic response with power-law relaxation. To test this idea, we developed a two-state model of crossbridge attachment and detachment. Unitary force was assigned when a crossbridge was attached, and an elastic force was generated when an attached crossbridge was displaced. Attachment rate, f(x), was spatially distributed with a total magnitude f0. Detachment rate was modeled as g(x) = g0+ g1x, where g0 is a constant and g1 indicates sensitivity to displacement. The analytical solution suggested that the exponential decay rate of phase 2 represents (f0 + g0) and the exponential rise rate of phase 3 represents g0. The depth of the nadir between phases 2 and 3 is proportional to g1. We prepared skinned mouse myocardium and applied a 1% stretch under varying concentrations of inorganic phosphate (Pi). The resulting force responses fitted the analytical solution well. The interpretations of phases 2 and 3 were consistent with lower f0 and higher g0 with increasing Pi. This novel scheme of interpreting the force response to a quick stretch does not require enhanced thin-filament activation and suggests that the myosin detachment rate is sensitive to stretch. Furthermore, the enhanced detachment rate is likely not due to the typical detachment mechanism following MgATP binding, but rather before MgADP release, and may involve reversal of the myosin power stroke.

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Section: Discussionmentioning

confidence: 94%

Enhancing diastolic function by strain-dependent detachment of cardiac myosin crossbridges

Palmer

Swank

Miller

et al. 2020

Journal of General Physiology

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“…The evidence for the myosin isoform mechanism comes from experiments where a myosin isoform [embryonic (EMB)] from a slow, cyclically contracting larval muscle was expressed in the minimally SA jump muscle, which rapidly shortens to power jumping. The EMB isoform exhibited increased F SA , F SA /F 0 , and power generation when expressed in jump muscle (74), essentially transforming a muscle with minimal SA to one with moderate SA. A critical component of this transformation was elevating [P i ], as increased SA properties were seen only above ϳ4 mM P i .…”

Section: Introductionmentioning

confidence: 99%

“…Our previous research with Drosophila muscle types suggests that there exist at least two different SA mechanisms, a myosin-isoform-based mechanism that differentiates muscles possessing minimal and moderate SA force generating ability and a thin filament-based mechanism that enables the even higher SA force-generating ability of IFM (17,73,74). The evidence for the myosin isoform mechanism comes from experiments where a myosin isoform [embryonic (EMB)] from a slow, cyclically contracting larval muscle was expressed in the minimally SA jump muscle, which rapidly shortens to power jumping.…”

Section: Introductionmentioning

confidence: 99%

A myosin-based mechanism for stretch activation and its possible role revealed by varying phosphate concentration in fast and slow mouse skeletal muscle fibers

Straight

Bell

Slosberg

et al. 2019

American Journal of Physiology-Cell Physiology

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Stretch activation (SA) is a delayed increase in force following a rapid muscle length increase. SA is best known for its role in asynchronous insect flight muscle, where it has replaced calcium’s typical role of modulating muscle force levels during a contraction cycle. SA also occurs in mammalian skeletal muscle but has previously been thought to be too low in magnitude, relative to calcium-activated (CA) force, to be a significant contributor to force generation during locomotion. To test this supposition, we compared SA and CA force at different Pi concentrations (0–16 mM) in skinned mouse soleus (slow-twitch) and extensor digitorum longus (EDL; fast-twitch) muscle fibers. CA isometric force decreased similarly in both muscles with increasing Pi, as expected. SA force decreased with Pi in EDL (40%), leaving the SA to CA force ratio relatively constant across Pi concentrations (17–25%). In contrast, SA force increased in soleus (42%), causing a quadrupling of the SA to CA force ratio, from 11% at 0 mM Pi to 43% at 16 mM Pi, showing that SA is a significant force modulator in slow-twitch mammalian fibers. This modulation would be most prominent during prolonged muscle use, which increases Pi concentration and impairs calcium cycling. Based upon our previous Drosophila myosin isoform studies and this work, we propose that in slow-twitch fibers a rapid stretch in the presence of Pi reverses myosin’s power stroke, enabling quick rebinding to actin and enhanced force production, while in fast-twitch fibers, stretch and Pi cause myosin to detach from actin.

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“…The roles of the alternative splicing variants of the Mhc gene in the enzymatic properties of myosin have been studied by transgenic replacement of the alternative exons in Drosophila (Bernstein & Milligan, 1997;Swank et al, 2001Swank et al, , 2003Swank et al, , 2004Miller et al, 2009;Ramanath et al, 2011;Zhao & Swank, 2013). For instance, exchanging exon-7a of the indirect flight muscle MHC with exon-7d of the embryonic body wall muscle MHC affected the ATPase activity, flight ability and filament structure, but not the actin-gliding velocity, suggesting that the ATP-lip encoded by the alternative exon-7 participates in the interaction of myosin and the nucleotide (Miller et al, 2005;Swank et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Alternative exon‐encoding regions of Locusta migratoria muscle myosin modulate the pH dependence of ATPase activity

et al. 2016

Insect Molecular Biology

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Whereas the vertebrate muscle myosin heavy chains (MHCs) are encoded by a family of Mhc genes, most insects examined to date contain a single Mhc gene and produce all of the different MHC isoforms by alternative RNA splicing. Here, we found that the migratory locust, Locusta migratoria, has one Mhc gene, which contains 41 exons, including five alternative exclusive exons and one differently included penultimate exon, and potentially encodes 360 MHC isoforms. From the adult L. migratoria, we identified 14 MHC isoforms (including two identical isoforms): four from flight muscle (the thorax dorsal longitudinal muscle), three from jump muscle (the hind leg extensor tibiae muscle) and seven from the abdominal intersegmental muscle. We purified myosins from flight muscle and jump muscle and characterized their motor activities. At neutral pH, the flight and the jump muscle myosins displayed similar levels of in vitro actin-gliding activity, whereas the former had a slightly higher actin-activated ATPase activity than the latter. Interestingly, the pH dependences of the actin-activated ATPase activity of these two myosins are different. Because the dominant MHC isoforms in these two muscles are identical except for the two alternative exon-encoding regions, we propose that these two alternative regions modulate the pH dependence of L. migratoria muscle myosin.

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An Embryonic Myosin Isoform Enables Stretch Activation and Cyclical Power in Drosophila Jump Muscle

Cited by 9 publications

References 53 publications

Enhancing diastolic function by strain-dependent detachment of cardiac myosin crossbridges

Enhancing diastolic function by strain-dependent detachment of cardiac myosin crossbridges

A myosin-based mechanism for stretch activation and its possible role revealed by varying phosphate concentration in fast and slow mouse skeletal muscle fibers

Alternative exon‐encoding regions of Locusta migratoria muscle myosin modulate the pH dependence of ATPase activity

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