Force, sarcomere shortening velocity and ATPase activity

Area of Science:

• Cardiovascular Physiology
• Muscle Mechanics
• Biochemistry

Background:

• Cardiac muscle contraction involves cross-bridge cycling between strong (force-generating) and weak states.
• Myosin isoforms (V1 and V3) in rat cardiac trabeculae exhibit different functional properties.
• Understanding the factors governing cross-bridge kinetics is crucial for cardiac function.

Purpose of the Study:

• To test if the transition rate of cardiac cross-bridges (XB) is a linear function of sarcomere velocity (VSL).
• To determine if myosin ATPase rates explain differences in unloaded shortening velocity (V0) between V1 and V3 isomyosins.

Main Methods:

• Induction of V1 (thyroid hormone) and V3 (PTU) isomyosins in rat trabeculae.
• Measurement of force and sarcomere length using strain gauges and laser diffraction.
• Analysis of force response to controlled shortening at constant VSL during twitch.

Main Results:

• Force decline during shortening showed a linear relationship with VSL, indicating VSL-dependent XB kinetics.
• The rate constant (G1) for force decline did not differ between V1 and V3 isomyosins.
• V0, ATPase rates, and actin-sliding velocities differed 2-2.5 fold between V1 and V3, suggesting isoform-specific differences beyond hydrolysis.

Conclusions:

• VSL-dependent feedback in XB kinetics provides an integrated model for cardiac mechanics and energetics.
• The hydrolytic domain of the cross-bridge is unlikely to solely determine V0.
• Further investigation into the actin-binding domain's role in cardiac sarcomere kinetics is warranted.