Our research is focused on the physiology and pathophysiology of skeletal muscle function. It aims at understanding how mechanisms involved in the control of skeletal muscle Ca2++ homeostasis and excitation-contraction (EC) coupling operate under normal and disease conditions. For this we use a combination of molecular biology, biochemistry, in vivo gene transfer and simultaneous electrophysiology and fluorescence detection on cultured cells and on single isolated differentiated muscle fibers.
Our research is focused on the physiology and pathophysiology of skeletal muscle function. It aims at understanding how specific mechanisms involved in the control of skeletal muscle Ca2+homeostasis and excitation-contraction (EC) coupling operate under normal and disease conditions. Muscle contraction is initiated when action potentials fired at the end-plate of the muscle cells propagate throughout the plasma membrane and trigger a conformational change of the CaV1.1 protein which gates open a Ca2+release channel (type 1 ryanodine receptor, RyR1) in the sarcoplasmic reticulum (SR) membrane. Ca2+then gets released from the SR into the cytosol and triggers contraction. Besides Ca2+release from the SR there is also Ca2+entry from the extracellular medium.
Our main current projects aim at:
1- Understanding basic mechanisms involved in the regulation of CaV1.1 and of RyR1 function.
2- Demonstrating how excitability and/or EC coupling are altered by specific disease mutations affecting the genes encoding CaV1.1, RyR1 and also other proteins involved in the function and/or maintenance of the EC coupling machinery.
The overall project stands on a set of methods and expertise that includes molecular biology and biochemistry, in vivo gene transfer and a state of the art combination of electrophysiology and fluorescence detection on single isolated differentiated muscle cells from mouse.
Institut NeuroMyoGène
UCBL – CNRS UMR 5310 – INSERM U1217
Faculté de Médecine et de Pharmacie – 3ème étage – Couloir AB
8 avenue Rockefeller
69008 Lyon
France