Inhibition of the ryanodine receptor calcium channel in the sarcoplasmic reticulum of skeletal muscle by an ADP/ATP translocase inhibitor, atractyloside

The effects of an inhibitor of ADP/ATP translocase (AAT) mainly expressed in the mitochondria inner membrane, atractyloside (ATR), on the gating property of the Ca2+ channels in the sarcoplasmic reticulum (SR) vesicles from the rabbit skeletal muscle were investigated using ion flux measurement and single channel recording. At 10 microM of cytoplasmic Ca2+, ATR decreased the rate constant of choline+ influx through the Ca2+ channels up to about 60% and perfectly inhibited about half the population of single Ca2+ channels incorporated into planar bilayers. Furthermore, the inhibition of the Ca2+ channels by ATR was effective at lower Ca2+. These results support the previous results that AAT exists in the skeletal muscle SR and plays a key role in the Ca2+ mobilization of the skeletal muscle cell [Yamaguchi, N., and Kasai, M. (1998) Biochem. J. 335, 541-547], and the number of Ca2+ channels regulated by AAT is thought to depend on the cytoplasmic Ca2+ concentration.