What is the clinical evidence from this study?

Intervention: Addition of 2 mM MgADP vs. Mg2+-free rigor solution containing 15 mM EDTA. Primary outcome: Rigor tension and in-phase stiffness.

What question did this study set out to answer?

To determine whether the conformational tilt linked to MgADP release in smooth muscle myosin directly drives mechanical force generation during the cross-bridge cycle.

July 1, 1999Biophysical JournalOpen Access

The ADP Release Step of the Smooth Muscle Cross-Bridge Cycle Is Not Directly Associated with Force Generation

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Key result

MgADP addition alters muscle rigor tension, suggesting S1 axial motion does not generate force.

Population

Permeabilized strips of chicken gizzard muscle, psoas muscle fibers, and soleus muscle fibers

Comparison

Addition of 2 mM MgADP vs Mg2+-free rigor solution containing 15 mM EDTA

Design

Preclinical

Authors

JDJody A. DantzigUniversity of Pennsylvania RBRobert BarsottiPhiladelphia College of Osteopathic Medicine SMScott ManzUniversity of Pennsylvania

Discussion

Member takes

Implication

Challenges assumed force-generating role of smooth muscle S1 motion; leaves open relevance to intact or human muscle mechanics.

Key Points

To determine whether the conformational tilt linked to MgADP release in smooth muscle myosin directly drives mechanical force generation during the cross-bridge cycle.
Measured mechanical tension and in-phase stiffness during 500-Hz sinusoidal length oscillations in permeabilized strips of chicken gizzard, psoas, and soleus muscles.
Assayed force responses upon the addition of 2 mM MgADP in rigor solutions across ionic strengths ranging from 50 to 200 mM, with and without thiophosphorylation of the myosin regulatory light chain.
Addition of 2 mM MgADP caused a slight increase in rigor tension in gizzard and soleus muscles, contrasting with a tension decrease in psoas muscle.
In-phase stiffness decreased across all three muscle types following 2 mM MgADP addition, showing reversible mechanical effects that were independent of ionic strength variations and myosin thiophosphorylation.

Structured PICO

Population

Permeabilized strips of chicken gizzard muscle, psoas muscle fibers, and soleus muscle fibers

Intervention

Addition of 2 mM MgADP

Comparator

Mg2+-free rigor solution containing 15 mM EDTA (rigor state)

Outcome

Rigor tension and in-phase stiffnesssurrogate

The axial motion of smooth muscle myosin subfragment 1 bound to actin upon dissociation of MgADP does not appear to be associated with force generation.

Limitations

Geometrical constraints of the intact contractile filament array may alter the motions of the myosin heads, explaining differences from previous structural studies.

Cite This Study

Dantzig et al. (1999) studied this question. Addition of 2 mM MgADP vs. Mg2+-free rigor solution containing 15 mM EDTA was evaluated on Rigor tension and in-phase stiffness. The addition of MgADP resulted in a slight increase in rigor tension in gizzard and soleus muscles but a decrease in psoas muscle, suggesting the axial motion of smooth muscle S1 upon MgADP dissociation is not associated with force generation.

synapsesocial.com/papers/6aa4389ee7e1fc2350749773 https://doi.org/10.1016/s0006-3495(99)76897-9

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The ADP Release Step of the Smooth Muscle Cross-Bridge Cycle Is Not Directly Associated with Force Generation

Discussion

Member takes

Implication

Key Points

Structured PICO

Limitations

Cite This Study

The ADP Release Step of the Smooth Muscle Cross-Bridge Cycle Is Not Directly Associated with Force Generation

Discussion

Member takes

Implication

Key Points

Structured PICO

Limitations

Cite This Study

Also Consider

Also Consider