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Related Experiment Videos

Cross-bridge dependent cooperativity determines the cardiac force-length relationship.

Carmit Levy1, Amir Landesberg

  • 1Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa.

Journal of Molecular and Cellular Cardiology
|April 8, 2006
PubMed
Summary

Cardiac muscle force generation is primarily driven by force itself, not sarcomere length or calcium levels. This finding reveals that cross-bridge recruitment directly determines cardiac cooperativity, impacting heart muscle function.

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Area of Science:

  • Cardiovascular Physiology
  • Muscle Mechanics
  • Biophysics

Background:

  • Cardiac muscle force regulation involves complex interactions between sarcomere length, intracellular calcium, and force generation.
  • The precise mechanism of cooperativity, particularly the dominant factor modulating these relationships, remains debated.

Purpose of the Study:

  • To investigate whether cardiac cooperativity is primarily dependent on sarcomere length, force, or calcium concentration.
  • To differentiate between length-dependent, force-dependent, and calcium-dependent hypotheses of cardiac cooperativity.

Main Methods:

  • Experiments were conducted on intact rat ventricular trabeculae under tetanized conditions.
  • Sarcomere length (SL) was manipulated, and force responses to imposed length oscillations were measured at varying extracellular calcium concentrations ([Ca(2+)](o)).

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  • Phase delay in force response relative to length oscillations was analyzed to determine the dependence on SL, force, and calcium.

    • Main Results:

    • Force responses exhibited a phase delay relative to length oscillations, particularly at shorter SL and lower [Ca(2+)](o), resulting in counterclockwise hysteresis.
    • The phase delay decreased with increasing SL or [Ca(2+)](o) when these were varied independently.
    • Crucially, maintaining constant force resulted in identical phase delays, irrespective of the SL and [Ca(2+)](o) combinations used.

    Conclusions:

    • Cardiac cooperativity is directly determined by the generated force, indicating that cross-bridge recruitment is force-dependent.
    • Sarcomere length and calcium concentration influence force indirectly by affecting the number of strongly bound cross-bridges.
    • The dominant mechanism of cardiac cooperativity relies on the number of strongly bound cross-bridges, directly regulated by force output.