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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Frank-Starling law of the heart describes the interrelationship between end-diastolic volume and cardiac ejection volume, a regulatory system that operates on a beat to beat basis. The overall goal of this research is to elucidate the structural mechanism(s) that underlie myofilament length dependent activation, the cellular mechanism responsible for Frank-Starling. To explore this hypothesis, the objective of the proposed research project is focused on answering the following questions that leads to two specific aims: 1) Is inter-filament spacing prior to active contraction the physiologically relevant parameter that determines myofilament Ca2+ responsiveness? It has been known for some time that active force development in skeletal muscle is associated with a change in inter-filament spacing AIM 1: to test the hypothesis that variation in inter-filament spacing with SL in active muscle underlies myofilament length dependent activation; furthermore determine under conditions of constant SL whether lattice spacing (LS) varies during activation, or remains constant as would be predicted by constant volume. Aim 2: Using isoproterenol, a compound that activates PKA phosphorylation, which has been shown to alter diastolic in vivo LS, test the dependence of LS during ¿-adrenergic stimulation