Stretch of Contracting Cardiac Muscle Abruptly Decreases the Rate of Phosphate Release at High and Low Calcium

Mansfield, Catherine; West, Tim G.; Curtin, N. A.; Ferenczi, Michael A.

doi:10.1074/jbc.m112.373498

Cited by 17 publications

(12 citation statements)

References 34 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our measurements of k tr in control phosphorylation are in the range observed in previous studies at maximal activation between ß4.5 and 14 s −1 with variance as a result of changes in temperature and muscle type (Wolff et al 1995;Fitzsimons et al 2001;Regnier et al 2004). Additionally, k tr at control phosphorylation levels (10-11 s −1 ) is close to the ATPase rate in trabeculae from rats under identical experimental conditions (ß8 s −1 ) (Mansfield et al 2012).…”

Section: The Effect Of Sarcomere Length On the Rate Of Force Productionsupporting

confidence: 82%

See 1 more Smart Citation

Revisiting Frank–Starling: regulatory light chain phosphorylation alters the rate of force redevelopment (k_tr) in a length‐dependent fashion

Toepfer

West

Ferenczi

2016

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

Key points Regulatory light chain (RLC) phosphorylation has been shown to alter the ability of muscle to produce force and power during shortening and to alter the rate of force redevelopment (k tr) at submaximal [Ca2+].Increasing RLC phosphorylation ∼50% from the in vivo level in maximally [Ca2+]‐activated cardiac trabecula accelerates k tr.Decreasing RLC phosphorylation to ∼70% of the in vivo control level slows k tr and reduces force generation. k tr is dependent on sarcomere length in the physiological range 1.85–1.94 μm and RLC phosphorylation modulates this response.We demonstrate that Frank–Starling is evident at maximal [Ca2+] activation and therefore does not necessarily require length‐dependent change in [Ca2+]‐sensitivity of thin filament activation.The stretch response is modulated by changes in RLC phosphorylation, pinpointing RLC phosphorylation as a modulator of the Frank–Starling law in the heart.These data provide an explanation for slowed systolic function in the intact heart in response to RLC phosphorylation reduction. AbstractForce and power in cardiac muscle have a known dependence on phosphorylation of the myosin‐associated regulatory light chain (RLC). We explore the effect of RLC phosphorylation on the ability of cardiac preparations to redevelop force (k tr) in maximally activating [Ca2+]. Activation was achieved by rapidly increasing the temperature (temperature‐jump of 0.5–20ºC) of permeabilized trabeculae over a physiological range of sarcomere lengths (1.85–1.94 μm). The trabeculae were subjected to shortening ramps over a range of velocities and the extent of RLC phosphorylation was varied. The latter was achieved using an RLC‐exchange technique, which avoids changes in the phosphorylation level of other proteins. The results show that increasing RLC phosphorylation by 50% accelerates k tr by ∼50%, irrespective of the sarcomere length, whereas decreasing phosphorylation by 30% slows k tr by ∼50%, relative to the k tr obtained for in vivo phosphorylation. Clearly, phosphorylation affects the magnitude of k tr following step shortening or ramp shortening. Using a two‐state model, we explore the effect of RLC phosphorylation on the kinetics of force development, which proposes that phosphorylation affects the kinetics of both attachment and detachment of cross‐bridges. In summary, RLC phosphorylation affects the rate and extent of force redevelopment. These findings were obtained in maximally activated muscle at saturating [Ca2+] and are not explained by changes in the Ca2+‐sensitivity of acto‐myosin interactions. The length‐dependence of the rate of force redevelopment, together with the modulation by the state of RLC phosphorylation, suggests that these effects play a role in the Frank–Starling law of the heart.

show abstract

Section: The Effect Of Sarcomere Length On the Rate Of Force Productionsupporting

confidence: 82%

“…Additionally, k tr at control phosphorylation levels (10–11 s −1 ) is close to the ATPase rate in trabeculae from rats under identical experimental conditions (∼8 s −1 ) (Mansfield et al . ).…”

Section: Discussionmentioning

confidence: 97%

Revisiting Frank–Starling: regulatory light chain phosphorylation alters the rate of force redevelopment (k_tr) in a length‐dependent fashion

Toepfer

West

Ferenczi

2016

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…From a mechanistic point of view, sarcomere give during relaxation and upon P i jump can both be explained by give stretching crossbridges and accelerating cross-bridge detachment via faster backwards cycling, i.e., by increasing f − app . This view is supported by the findings in fibre studies that stretch rapidly reduces the rate of P i release, inducing redistribution of cross-bridges towards ADP.P i -binding states (Mansfield et al 2012). The fast cross-bridge detachment in the lengthening (give) sarcomeres reduces the load in the serially connected other sarcomeres and therein promotes cross-bridge detachment via fast forwards cycling by increasing g app (Stehle et al 2009).…”

Section: Differences Of Force Decay Upon [P I ] and [Ca 2+ ] Changes mentioning

confidence: 71%

Kinetic coupling of phosphate release, force generation and rate-limiting steps in the cross-bridge cycle

Stehle

Tesi

2017

J Muscle Res Cell Motil

View full text Add to dashboard Cite

A basic goal in muscle research is to understand how the cyclic ATPase activity of cross-bridges is converted into mechanical force. A direct approach to study the chemo-mechanical coupling between P release and the force-generating step is provided by the kinetics of force response induced by a rapid change in [P]. Classical studies on fibres using caged-P discovered that rapid increases in [P] induce fast force decays dependent on final [P] whose kinetics were interpreted to probe a fast force-generating step prior to P release. However, this hypothesis was called into question by studies on skeletal and cardiac myofibrils subjected to P jumps in both directions (increases and decreases in [P]) which revealed that rapid decreases in [P] trigger force rises with slow kinetics, similar to those of calcium-induced force development and mechanically-induced force redevelopment at the same [P]. A possible explanation for this discrepancy came from imaging of individual sarcomeres in cardiac myofibrils, showing that the fast force decay upon increase in [P] results from so-called sarcomere 'give'. The slow force rise upon decrease in [P] was found to better reflect overall sarcomeres cross-bridge kinetics and its [P] dependence, suggesting that the force generation coupled to P release cannot be separated from the rate-limiting transition. The reasons for the different conclusions achieved in fibre and myofibril studies are re-examined as the recent findings on cardiac myofibrils have fundamental consequences for the coupling between P release, rate-limiting steps and force generation. The implications from P-induced force kinetics of myofibrils are discussed in combination with historical and recent models of the cross-bridge cycle.

show abstract

“…Such a straindependent 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). Our own observations with increasing Pi concentration are consistent with the idea that Pi acts to enhance crossbridge detachment rate, i.e., g 0 in our model, as noted by a positive correlation between g 0 and Pi in Table 1.…”

Section: Discussionmentioning

confidence: 93%

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

Palmer

Swank

Miller

et al. 2020

Journal of General Physiology

View full text Add to dashboard Cite

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.

show abstract

Stretch of Contracting Cardiac Muscle Abruptly Decreases the Rate of Phosphate Release at High and Low Calcium

Cited by 17 publications

References 34 publications

Revisiting Frank–Starling: regulatory light chain phosphorylation alters the rate of force redevelopment (k_tr) in a length‐dependent fashion

Revisiting Frank–Starling: regulatory light chain phosphorylation alters the rate of force redevelopment (k_tr) in a length‐dependent fashion

Kinetic coupling of phosphate release, force generation and rate-limiting steps in the cross-bridge cycle

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

Contact Info

Product

Resources

About

Stretch of Contracting Cardiac Muscle Abruptly Decreases the Rate of Phosphate Release at High and Low Calcium

Cited by 17 publications

References 34 publications

Revisiting Frank–Starling: regulatory light chain phosphorylation alters the rate of force redevelopment (ktr) in a length‐dependent fashion

Revisiting Frank–Starling: regulatory light chain phosphorylation alters the rate of force redevelopment (ktr) in a length‐dependent fashion

Kinetic coupling of phosphate release, force generation and rate-limiting steps in the cross-bridge cycle

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

Contact Info

Product

Resources

About

Revisiting Frank–Starling: regulatory light chain phosphorylation alters the rate of force redevelopment (k_tr) in a length‐dependent fashion

Revisiting Frank–Starling: regulatory light chain phosphorylation alters the rate of force redevelopment (k_tr) in a length‐dependent fashion