Emodin‐induced muscle contraction of mouse diaphragm and the involvement of Ca 2+ influx and Ca 2+ release from sarcoplasmic reticulum

1 The effects on skeletal muscle of emodin, an anthraquinone, were studied in the mouse isolated diaphragm and sarcoplasmic reticulum (SR) membrane vesicles. 2 Emodin dose‐dependently caused muscle contracture, simultaneously depressing twitch amplitude. Neither tubocurarine nor tetrodotoxin blocked the contraction suggesting that it was caused myogenically. 3 The contraction induced by emodin persisted in a Ca 2+ free medium with a slight reduction in the maximal force of contraction. The contraction induced by emodin in the Ca 2+ free medium was completely blocked when the internal Ca 2+ pool of the muscle was depleted by ryanodine. These data suggest that the contraction caused by emodin is due to the release of Ca 2+ from the intracellular ryanodine‐sensitive pool. 4 In contrast to the effect seen in the Ca 2+ free medium, emodin induced a small but consisted contraction in the ryanodine‐treated muscle in Krebs medium. The contraction was blocked in the presence of dithiothreitol and was partially blocked by nifedipine, suggesting that oxidation of a sulphhydryl group on the external site of dihydropyridine receptor is involved. 5 Emodin dose‐dependently increased Ca 2+ release from actively loaded SR vesicles and this effect was blocked by ruthenium red, a specific Ca 2+ release channel blocker, and the thiol reducing agent, DTT, suggesting that emodin induced Ca 2+ release through oxidation of the critical SH of the ryanodine receptor. 6 [ 3 H]‐ryanodine binding was dose‐dependently potentiated by emodin in a biphasic manner. The degree of potentiation of ryanodine binding by emodin increased dose‐dependently at concentrations up to 10 μ M but decreased at higher concentrations of 10–100 μ M . 7 These data suggest that muscle contraction induced by emodin is due to Ca 2+ release from the SR of skeletal muscle, as a result of oxidation of the ryanodine receptor and influx of extracellular Ca 2+ through voltage‐dependent Ca 2+ channels of the plasma membrane.British Journal of Pharmacology (1998) 123 , 815–820; doi: 10.1038/sj.bjp.0701677