Cation pumps in skeletal muscle: potential role in muscle fatigue

Two membrane bound pumps in skeletal muscle, the sarcolemma Na+-K+ adenosine triphosphatase (ATPase) and the sarcoplasmic reticulum Ca2+-ATPase, provide for the maintenance of transmembrane ionic gradients necessary for excitation and activation of the myofibrillar apparatus. The rate at which the pumps are capable of establishing ionic homeostasis depends on the maximal activity of the enzyme and the potential of the metabolic pathways for supplying adenosine triphosphate (ATP). The activity of the Ca2+-ATPase appears to be expressed in a fibre type specific manner with both the amount of the enzyme and the isoform type related to the speed of contraction. In contrast, only minimal differences exist between slow-twitch and fast-twitch fibres in Na+-K+ ATPase activity. Evidence is accumulating that both active transport of Na+ and K+ across the sarcolemma and Ca2+-uptake by the sarcoplasmic reticulum may be impaired in vivo in a task specific manner resulting in loss of contractile function. In contrast to the Ca2+-ATPase, the Na+-K+ ATPase can be rapidly upregulated soon after the onset of a sustained pattern of activity. Similar programmes of activity result in a downregulation of Ca2+-ATPase but at a much later time point. The manner in which the metabolic pathways reorganize following chronic activity to meet the changes in ATP demand by the cation pumps and the degree to which these adaptations are compartmentalized is uncertain.