Role of stretch-induced structural changes in the myofilaments in the length-dependent activation of cardiac muscle

A healthy heart produces a stronger contraction in response to increased venous filling, a response known as the Frank-Starling relationship. Despite decades of investigation at the cellular level, the molecular basis of this so-called “length-dependent activation” (LDA) in cardiac muscle is still unclear. Here we will use a combination of mechanical protocols and small-angle X-ray diffraction at ID02 on electrically paced muscle tissue isolated from the rat heart to determine the dynamic structural changes in the constituent myosin and actin filaments induced by an increase in muscle length during the relaxed phase of the cardiac cycle. 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.