Lecture „The role of ryanodine receptors in muscle function“

Ryanodine receptors (RyR) are the Ca2+ release channel of skeletal muscle, which are responsible for rapidly releasing a large amount of Ca2+ upon electrical stimulation to evoke contraction. In the resting muscle, RyR leak Ca2+ and require the expenditure of energy to maintain steady state Ca2+ content of the intracellular Ca2+ store. It is this function that regulates multiple processes in the muscle, including the regulation of Ca2+ permeability of the plasma membrane and distribution of Ca2+ across the intracellular compartments, non-shivering thermogenesis and adaptation to changes in muscle activity. In this talk I will describe how RyR basal function controls the movements of Ca2+ between cellular compartments following changes in the RyR due to mutations, intense exercise and changes in activity. To do this I will present novel techniques for measuring Ca2+ movements and heat generation within the fibre that we have used in conjunction with muscle from transgenic mice and fibres isolated from biopsies of human muscle.