Ca2+ accumulation and cell damage in skeletal muscle during low frequency stimulation

Abstract

Electrical stimulation has been shown to produce a marked increase in Ca2+ influx and Ca2+ content in rat skeletal muscle. Long-term low-frequency stimulation (1 Hz, 240 min) increased 45Ca uptake by 30% and 154% in soleus and extensor digitorum longus muscles, respectively. Studies using Ca2+-fluorescent dyes have shown that intracellular concentrations of free Ca2+ are increased up to threefold during long-term low-frequency stimulation, suggesting that muscle cells have difficulties in handling the Ca2+ taken up during stimulation. Furthermore, long-term low-frequency stimulation induces leakage of the intracellular enzyme lactate dehydrogenase from the muscles. This leakage may reflect degradation of membrane proteins by the Ca2+-activated neutral protease calpain. This, in turn, leads to further influx of Ca2+ and further acceleration of protein breakdown. Membrane leakages are likely to result in sensations of pain in the damaged muscle. It is suggested that Ca2+ plays a central role in the development of muscle fibre injury during prolonged muscle activity of workers using a computer mouse.