Molecular basis of length-dependent activation in cardiac muscle

The efficiency of the heart as a pump depends on an auto-regulatory mechanism, called length-dependent activation (LDA), that potentiates the strength of contraction in response to an increase in ventricular filling. Despite decades of investigation, the molecular basis of LDA in cardiac muscle is still unclear. Here we propose to use X-ray diffraction at the upgraded beamline ID02 to investigate the structural changes in the myofilaments induced by stretch in relaxed and partially calcium-activated demembranated cardiac trabeculae in near-physiological conditions. Because the disruption of LDA is a common pathogenic mechanism underlying cardiac dysfunction, the results of this research will provide new targets and assays for the development of new pharmacological approaches to treat heart failure in cardiac diseases.