Calcium signaling and function of the sarcomere in cardiac and skeletal muscle
During the past years our studies have converged to the observations that metabolic impairment and reactive oxygen species (ROS) production directly affect excitation-contraction coupling (ECC) both in cardiac and skeletal muscle, in ischemic cardiomyopathy as well as inherited pathologies. Our goal is to perform fundamental and clinical research studies in order to investigate the early signaling pathways leading to striated muscular contraction alterations during pathologies such as myocardial ischemia, ventilation-induced dysfunction and muscular dystrophies. Our research uses technics ranging from in vivo (echocardiogram, electrocardiogram) to in vitro methods at the organ, cellular and sub-levels level allowing for exploration of calcium signaling, mitochondrial activity and sarcomeric function in cardiac and skeletal muscles.
Theme 1 : Pathophysiological interaction between mitochondria and endo/sarcoplasmic reticulum
In the heart, contraction is initiated by the propagation of an action potential on the cell surface, which corresponds to a rapid and transient membrane depolarization of the myocytes. During an action potential, Ca2+ ions enter into the cells and open a channel called the …………………. (See More).
Theme 2 : Characterization of DMD and CPVT patient-specific cardiomyocytes derived from induced pluripotent stem cells
It is now possible to reprogram human cells from skin, blood and urine to cardiomyocytes. Our team uses this new cellular tool to investigate human genetic diseases affecting the heart (stress-induced arrhythmias and Duchenne muscular dystrophy)……. (See more)
Theme 3 : Regional impairment of myocardial contractility: in vivo – sarcomeric function relationship
The contractile activity of the heart is scalable. Furthermore neurohormonal regulation, myocardial contractility can be directly modified by the filling volume of the ventricles. Thus, the increased blood volume puts pressure (stress) on the walls, pressure transmitted to the myofibrils to alter their contractile properties. This is the myocardium Frank-Starling law characterized on myocytes by tension – length relationship. The heart uses this relationship to regulate cardiac output more particularly during exercise and its alteration contributes to heart failure state…………………. (See more)
Theme 4 : Myopathy induced by intensive care and anesthesia
Intensive care presents several constraints on peripheral and respiratory muscle such as unloading, mechanical ventilation, drug toxicity or sepsis, leading to major contractile dysfunction. This myopathy, characterized by the presence of atrophy and injury, is generally observed in …………………………. (See more)