Electrical interval stimulation improves calcium handling rapidly but transiently in isolated mouse soleus muscle

Abstract

Running wheel training in mice involves burst activity and boosts cellular capacity for cation homeostasis in hindlimb muscles (de Snoo, FASEB J 19:A132, 2005). Here, we investigated what biochemical mechanism underlies improved calcium handling in soleus muscle. Soleus (SOL) of 6-wks trained and control C57Bl/6 mice were ligated at the tendons, tied to a force transducer, and set at resting length. Baseline force (BLF) was used as index of free calcium. First, a 300 s bout of 6 Hz stimulation was recorded. BLF increased in control SOL to 5-fold higher levels than in trained SOL. Next, a short-term training protocol mimicking mouse running activity was executed consisting of four sets, separated by 60 s rest, of ten 10 s trains (duty cycle 0.5) of 6 Hz stimulation. In set I, train 1, BLF steeply increased in control SOL as before. During trains 2–10, BLF remained higher in control though markedly less pronounced. In set II, the same result was found. In set III, however, changes in peak- and baseline force were identical for control and trained SOL from train 6 on. In set IV, this result was found from train 3 on. During a next 150 s bout of 6 Hz stimulation control and trained SOL mechanically performed identically. This acquired ‘short-term training’ property was lost after 600 s of rest in control, but not trained SOL. These results may be explained by transient activation of the cAMP-PKA pathway transiently boosting calcium pumping via disinhibition of SERCA2A through phospholamban phosphorylation.