Team: Excitability and calcium signaling in normal and diseased skeletal muscle

About

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.

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 Ca_V1.1 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.

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.