What question did this study set out to answer?

This research investigates how strong binding of myosin affects calcium sensitivity and isometric tension based on sarcomere length.

September 21, 1998Circulation ResearchOpen Access

Strong Binding of Myosin Modulates Length-Dependent Ca 2+ Activation of Rat Ventricular Myocytes

Q: What is the clinical evidence from this study?

Study design: Other. Intervention: N-ethylmaleimide-modified myosin subfragment 1 (NEM-S1) vs. Control myocytes (absence of NEM-S1). Primary outcome: Ca2+ sensitivity of tension (pCa50).

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Key result

Application of NEM-S1 to rat ventricular myocytes increased Ca2+ sensitivity (pCa50 increased from 5.40 to 5.52) and eliminated the sarcomere length dependence of Ca2+ sensitivity.

Population

Single ventricular myocytes isolated by enzymatic digestion of rat hearts and subsequently rapidly skinned

Comparison

N-ethylmaleimide-modified myosin subfragment 1 vs Control myocytes (absence of NEM-S1)

Design

Preclinical

Authors

DFDaniel P. FitzsimonsUniversity of Idaho RMRichard L. MossUniversity of Vermont

Discussion

Member takes

Implication

Supports thin filament cooperativity in length-dependent activation; hypothesis-generating for sarcomere-targeted therapies.

Key Points

This research investigates how strong binding of myosin affects calcium sensitivity and isometric tension based on sarcomere length.
Ventricular myocytes were isolated from rat hearts through enzymatic digestion and rapidly skinned.
Maximal tension and calcium sensitivity (pCa50) were measured with and without N-ethylmaleimide-modified myosin subfragment 1 (NEM-S1) at varying sarcomere lengths.
The effect of NEM-S1 on submaximal calcium-activated tensions at short and long sarcomere lengths was analyzed.
Application of NEM-S1 at approximately 1.90 microm sarcomere length increased pCa50 from 5.40±0.02 to 5.52±0.02 pCa units.
NEM-S1 treatment eliminated the length dependence of calcium sensitivity; the difference in pCa50 between short and long lengths was reduced to 0.02±0.01 compared to 0.10±0.01 in controls.
The findings suggest that decreased cooperative activation of the thin filament at short sarcomere lengths is primarily due to fewer strong-binding crossbridges.

Structured PICO

Population

Single ventricular myocytes isolated from rat hearts to study sarcomere length and Ca2+ sensitivity.

Intervention

N-ethylmaleimide-modified myosin subfragment 1 (NEM-S1)

Comparator

Control myocytes (absence of NEM-S1)

Outcome

Maximal tension and Ca2+ sensitivity of tension (pCa50) at short and long sarcomere lengthssurrogate

Main Result

Absolute Event Rate: 5.52% vs 5.4%

The decrease in Ca2+ sensitivity of tension at short sarcomere lengths results predominantly from decreased cooperative activation of the thin filament due to fewer strong-binding crossbridges.

Cite This Study

Fitzsimons et al. (1998) studied this question. N-ethylmaleimide-modified myosin subfragment 1 (NEM-S1) vs. Control myocytes (absence of NEM-S1) was evaluated on Ca2+ sensitivity of tension (pCa50). Application of NEM-S1 to rat ventricular myocytes increased Ca2+ sensitivity (pCa50 increased from 5.40 to 5.52) and eliminated the sarcomere length dependence of Ca2+ sensitivity.

synapsesocial.com/papers/6a63c72994d8bae735b3620c https://doi.org/10.1161/01.res.83.6.602

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Strong Binding of Myosin Modulates Length-Dependent Ca 2+ Activation of Rat Ventricular Myocytes

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Strong Binding of Myosin Modulates Length-Dependent Ca 2+ Activation of Rat Ventricular Myocytes

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Also Consider

Also Consider