Signalling mechanisms in skeletal muscle: role in substrate selection and muscle adaptation

Exercise produces a multitude of time- and intensity-dependent physiological, biochemical and molecular changes within skeletal muscle. With the onset of contractile activity, cytosolic and mitochondrial [Ca²⁺] levels are rapidly increased and, depending on the relative intensity of the exercise, metabolite concentrations change (i.e. increases in [ADP] and [AMP], decreases in muscle creatine phosphate and glycogen). These contraction-induced metabolic disturbances activate several key kinases and phosphatases involved in signal transduction. Important among these are the calcium dependent signalling pathways that respond to elevated Ca²⁺ concentrations (including Ca²⁺/calmodulin-dependent kinase, Ca²⁺-dependent protein kinase C and the Ca²⁺/calmodulin-dependent phosphatase calcineurin), the 5′-adenosine monophosphate-activated protein kinase, several of the mitogen-activated protein kinases and protein kinase B/Akt. The role of these signal transducers in the regulation of carbohydrate and fat metabolism in response to increased contractile activity has been the focus of intense research efforts during the past decade.