Skeletal muscle energy turnover can increase more than 100 fold during high intensity exercise. Thus, it is vitally important for muscle cells to possess signalling systems that keep the balance between ATP-utilisation and ATP-production. However, little is know about the mechanism whereby the muscle energy level or ATP-generating capacity restrains the rate of ATP- utilisation. Here is presented such a system where events in the excitation-contraction (EC) coupling are affected by glycogen content and localisation. We used a mechanically-skinned muscle fibre preparation where the fibre structural integrity and excitability is maintained, and one can keep the energy level (ATP and PCr) high and constant while varying glycogen levels. Data from this preparation strongly indicates that glycogen has a structural, non-metabolic, role in maintaining normal sarcoplasmic reticulum (SR) Ca²⁺ regulation in mammalian skeletal muscle. Further, measurements of SR function following experimentally manipulation of muscle glycogen at both the isolated muscle and human whole body level, strongly supports that glycogen has a structural role in maintaining normal EC coupling in mammalian skeletal muscle, by modulating SR Ca²⁺ regulation. In addition, we have shown that skeletal muscle force depression due to ionic perturbations, and subsequent reduced SR Ca²⁺ release, is affected by muscle energy status (Macdonald et al. 2007). Further, in isolated muscles and single fibres, loss of excitability can be partly reversed by the lactate ion by closing Cl-channels. In conclusion, these findings illustrate how energy level modulates skeletal muscle EC coupling by affecting SR Ca²⁺ handling and excitability. Macdonald, W.A., Ørtenblad, N. & Nielsen, O.B. 2007. Am J Physiol 292, E771-E778.