Biophysical Society Thematic Meeting | Canterbury 2023

Towards a More Perfect Union: Multi-Scale Models of Muscle and Their Experimental Validation

Monday Speaker Abstracts

STRUCTURAL DYNAMICS OF THE THICK FILAMENT DURING THE PHYSIOLOGICAL CARDIAC CYCLE. Yanhong Wang 1 ; Luca Fusi 1 ; Jesus G Ovejero 1 ; Cameron Hill 1 ; Samina Juma 1 ; Flair Paradine Cullup 1 ; So-Jin Park-Holohan 1 ; Theyencheri Narayanan 2 ; Malcolm Irving 1 ; Elisabetta Brunello 1 ; 1 King's College London , London, United Kingdom 2 European Synchrotron Radiation Facility, Grenoble, France The contraction of heart muscle is regulated by a dual-filament mechanism in which calcium dependent structural changes in the actin-containing thin filaments control the number of accessible binding sites for the myosin motors, while regulatory changes in the myosin containing thick filaments modulate the number of available motors and the kinetics of force development and relaxation. Here we investigated the structural dynamics of the thick filament in electrically-paced cardiac trabeculae isolated from rat hearts using a combination of time resolved small-angle X-ray diffraction and mechanical protocols that reproduce the four phases of the physiological cardiac cycle: isometric contraction, ejection, isometric relaxation and refilling. Sarcomere length was maintained at the diastolic value during active force development, shortened by 12% while force was held at ∼ 50 kPa, was held constant during the first phase of relaxation, before being re-stretched to the initial value at the end of mechanical relaxation. The force-sarcomere length relationship in this protocol mimics the pressure-volume relationship in the intact heart, and the associated regulatory structural changes in the thick filament and myosin motors represent a first step towards understanding the role of myosin based regulation in the control of the physiological cardiac cycle. Supported by BHF, Wellcome Trust (UK), and ESRF (France).

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