After excitation of skeletal muscle, the disturbed ion homeostasis is restored by Na⁺, K⁺ ATPase of the sarcolemma and Ca²⁺ ATPase of the sarcoplasmic reticulum (SR). Contrary to Na⁺, K⁺ ATPase, the concentration and isoenzyme distribution of SR Ca²⁺ ATPase in human skeletal muscle depend on fibre type and age. In cultured human muscle cells the concentration and activity of Na⁺, K⁺ ATPase and SR Ca²⁺ ATPase increase with maturation.

In skeletal muscle and cultured muscle cells of patients suffering from myotonic dystrophy (MyD), the activity and the concentration of both Na⁺, K⁺ ATPase and SR Ca²⁺ ATPase are decreased by about 40%. In addition, we measured in cultured MyD muscle cells at rest an increased cytosolic Ca²⁺ concentration ([Ca²⁺]_i) caused by active voltage‐operated Ca²⁺ channels, which are inactive in resting control cells. However, the restoration of a stimulus‐induced Ca²⁺ transient is unaffected. A differentiation‐related disturbance of membranes or a modulation defect of membrane proteins may play a role in MyD.

In skeletal muscle and cultured muscle cells of patients suffering from Brody's disease, which is characterized by impaired muscle relaxation, the SR Ca²⁺ ATPase activity is reduced by about 50%, but the concentrations of total SR Ca²⁺ ATPase and the predominant SERCA1 isoform are normal. Diseased muscle cells show a delayed restoration of [Ca²⁺]_i after stimulation, which might be explained by structural modifications of SERCA1. Reduction of the Ca²⁺ release by drugs balances the excitation–relaxation cycle of the pathological cells.