Activation dependence of stretch activation in mouse skinned myocardium: implications for ventricular function

Area of Science:

• Cardiovascular Physiology
• Cardiac Mechanics
• Muscle Biophysics

Background:

• Ventricular ejection may be augmented by stretch activation, a delayed force development in the ventricular wall.
• This phenomenon is linked to ventricular torsion and its importance in cardiac function warrants further investigation.

Purpose of the Study:

• To characterize the stretch activation response in murine myocardium.
• To determine the dependence of stretch activation on calcium (Ca2+) concentration.
• To elucidate the role of cross-bridge binding in the stretch activation mechanism.

Main Methods:

• Murine skinned myocardium was studied at 22°C in solutions with varying Ca2+ concentrations.
• Stretch activation was induced by imposing controlled stretches (0.5-2.5%) on isometrically contracting muscle.
• The effect of NEM-S1, a myosin subfragment 1 derivative, on stretch activation was assessed.

Main Results:

• The force response to stretch was multiphasic, including a delayed force redevelopment characteristic of stretch activation.
• The amplitude and rate of stretch activation were modulated by Ca2+ concentration and pre-stretch isometric force.
• NEM-S1 treatment accelerated the rate and reduced the amplitude of stretch activation at submaximal forces.

Conclusions:

• Myocardial stretch activation's rate and amplitude are dependent on the level of activation.
• Stretch activation involves cooperative binding of cross-bridges to the thin filament.
• This mechanism likely contributes to enhanced systolic ejection during excitation-contraction coupling.