Modulation by prednisolone of calcium handling in skeletal muscle cells

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Abstract
Increased calcium (Ca2+) influx has been incriminated as a potential pathological mechanism in the chronic skeletal muscle degeneration exhibited by Duchenne muscular dystrophy (DMD) patients. We have studied the influence of the glucocorticoid α‐methylprednisolone (PDN), the only drug known to have a beneficial effect on the degenerative course of DMD, on Ca2+ handling in the C2 skeletal muscle cell line. PDN, when added 3 days (when myoblasts start to fuse into myotubes) after cell seeding, led to a 2 to 4 fold decrease in cellular Ca2+ uptake. This decrease was independent of the extracellular Ca2+ concentration applied to cells. The effect took at least 24 h in order to become established (PDN of 10−5 m) and took longer for lower PDN concentrations (EC50 of ca. 10−6 m at day 5, 10−6 5 m at day 7 and 10−7 5 m at day 9 in culture). Cellular calcium accumulation was also decreased in PDN‐treated myotubes exposed to 45Ca2+‐containing medium for 1 to 6 days. No effect of PDN was seen on 45Ca2+ efflux; a decrease in the amount of 45Ca2+released was observed due to the reduction of cellular 45Ca2+ loading. PDN treatment led to an approximately 2 fold decrease in basal cytosolic Ca2+ concentration. 6 Three antioxidant drugs (lazaroids), previously shown to enhance in vitro skeletal muscle cell differentiation to the same extent as PDN, induced a similar decrease in Ca2+ influx. 7 Our results suggest that long‐term incubation of C2 cells with PDN leads to a decrease of the size of the cellular Ca2+ pools and to reduced resting cytosolic Ca2+ levels. Part of the beneficial effect of PDN in DMD patients could be attributed to a reduction of Ca2+ influx and of the size of Ca2+ pools in dystrophic muscle fibres.