TIME-RESOLVED X-RAY DIFFRACTION OF CARDIAC MUSCLE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The so-called "Frank Starling Law of the Heart" describes the relationship between end-diastolic volume and cardiac ejection volume that is the major regulatory system operating on a beat to beat basis in the adult heart. The main cellular mechanism that underlies this phenomenon is an increase in the responsiveness of cardiac myofilaments to activating Ca2+ ions at longer sarcomere lengths. The fundamental mechanism responsible for this increase in responsiveness has been elusive despite considerable experimental scrutiny by various research groups. This project we aim to determine the structural mechanisms behind this phenomenon. We obtain two-dimensional x-ray diffraction patterns from electrically stimulated, continuously twitching, rat cardiac muscle . We are particularly interested in structural changes that occur with changes in muscle length under diastolic conditions that can be related to subsequent force production. We examine the relative position of the heads to the thin filaments (via the I11/I10 equatorial intensity ratio), the radial extent of the heads from the center of the thick filament backbones (from the myosin layer lines), strain in the thick filament backbones (from the spacing of the m6 meridional reflection), and the orientation of the myosin heads around the normal to the thick filament long axis (m3 reflection intensity). Any of these factors could be expected to affect force production if they change as a function of sarcomere length.