Prednisolone-induced muscle dysfunction is caused more by atrophy than by altered acetylcholine receptor expression.

Large doses of glucocorticoids can alter muscle physiology and susceptibility to neuromuscular blocking drugs by mechanisms not clearly understood. We investigated the effects of moderate and large doses of prednisolone on muscle function and pharmacology, and their relationship to changes in muscle size and acetylcholine receptor (AChR) expression. With institutional approval, 35 Sprague-Dawley rats were randomly allocated to receive daily subcutaneous doses of 10 mg/kg prednisolone (P10 group), 100 mg/kg prednisolone (P100 group), or an equal volume of saline (S group) for 7 days. A fourth group of rats was pair fed (food restricted) with the P100 rats for 7 days (FR group). On Day 8, the nerve-evoked peak twitch tensions, tetanic tensions, and fatigability, and the dose-response curves of d-tubocurarine in the tibialis cranialis muscle were measured in vivo and related to muscle mass or expression of AChRs. Rate of body weight gain was depressed in the P100, FR, and P10 groups compared with the S group. Tibialis muscle mass was smaller in the P100 group than in the P10 or S groups. The evoked peak twitch and tetanic tensions were less in the P100 group than in the P10 or S groups, however, tension per milligram of muscle mass was greater in the P100 group than in the S group. The 50% effective dose of d-tubocurarine (microg/kg) in the tibialis muscle was smaller in the P10 (33.6 +/- 5.4) than in the S (61.9 +/- 5.0) or the P100 (71.3 +/- 9.6) groups. AChR expression was less in the P10 group than in the S group. The evoked tensions correlated with muscle mass (r(2) = 0.32, P < 0.001), however, not with expression of AChR. The 50% effective dose of d-tubocurarine did not correlate with muscle mass or AChR expression. Our results suggest that the neuromuscular dysfunction after prednisolone is dose-dependent, and derives primarily from muscle atrophy and derives less so from changes in AChR expression.

CONCLUSIONS

The mechanisms by which chronic glucocorticoid therapy alters neuromuscular physiology and pharmacology are unclear. We suggest that the observed effects are dose-dependent and derive primarily from muscle atrophy and derive less from changes in acetylcholine receptor expression.