The smooth muscle cross-bridge cycle studied using sinusoidal length perturbations.

Area of Science:

• Biophysics
• Muscle Physiology
• Biochemistry

Background:

• Smooth muscle exhibits distinct mechanical properties: phasic (fast-contracting) and tonic (slow-contracting).
• The underlying cross-bridge cycle mechanisms contributing to these differences remain incompletely understood.

Purpose of the Study:

• To investigate if variations in cross-bridge cycling and states explain the mechanical differences between phasic and tonic smooth muscle.
• To elucidate the roles of inorganic phosphate (P(i)) and magnesium-adenosine diphosphate (MgADP) in smooth muscle force production.

Main Methods:

• Used Triton-permeabilized rabbit portal vein (phasic) and aorta (tonic) smooth muscle strips.
• Oscillated muscle strips from 1 to 100 Hz to measure force and stiffness as a function of frequency.
• Examined the effects of elevated inorganic phosphate (P(i)) and MgADP on steady-state force and stiffness during calcium activation.

Main Results:

• In phasic portal vein, elevated P(i) reduced force and stiffness proportionally, indicating P(i) release is linked to cross-bridge attachment.
• In tonic aorta, elevated P(i) reduced force more than stiffness, suggesting an attached actin-myosin-ADP-P(i) state.
• In portal vein, elevated MgADP reduced stiffness but not force, while in aorta, it reduced both proportionally, implicating MgADP release in tonic muscle force production.

Conclusions:

• Phasic smooth muscle (portal vein) likely produces force after P(i) release but before MgADP release.
• Tonic smooth muscle (aorta) associates a portion of its force production with MgADP release during the cross-bridge powerstroke.
• These distinct cross-bridge kinetics contribute to the observed mechanical differences between phasic and tonic smooth muscle types.