Ca2+ dependent processes in skeletal muscle

Skeletal muscle function is both tightly regulated and dictated by transient changes in the intracellular calcium concentrations via a process called excitation-contraction coupling. As well as controlling the production of muscle force, calcium can trigger other calcium dependent events including cellular signalling and the activation of calcium dependent proteases, calpains.

Our lab is interested in understanding an array of calcium dependent processes in skeletal muscle. Specific projects include the investigation of calpains, where we aim to help understand their regulation and functional properties in skeletal muscle. Overall, we aim to consider physiologically relevant circumstances. As an example, we use exercise as a manipulation to alter intracellular calcium levels. Exercise can also be used to see how stretching a muscle (i.e. lengthening, or eccentric contractions) can affect the activation of calpains and the abundance and/or movement of their in vivo cellular targets. Of importance, if an individual has an absent or non-functional muscle specific calpain-3, they develop a type of muscular dystrophy (LGMD2A).

Other proteins important for excitation-contraction coupling and of interest to us in both skeletal and cardiac muscle include the ryanodine receptor, the dihydropyridine receptor, the sarcoplasmic reticulum Ca2+-ATPase (SERCA) and calsequestrin (CSQ). In collaboration with Professor Graham Lamb, Department of Physiology, Anatomy and Microbiology at La Trobe University, as well as researchers at Victoria University, we investigate how age, disease and exercise training affect the function and abundance of these proteins.