Dithiothreitol (DTT), at 50-100 mM, induced a phasic reversible contraction of frog skeletal muscle. 2. Exposure of single fibers to nifedipine (20 microM), an L-type Ca2+ antagonist, blocked the twitch and tetanus tensions but never affected the DTT-induced contraction. 3. DTT also produced a phasic contraction in fibers where voltage sensors were inactivated in the presence of high K+ concentration (190 mM). 4. A fiber was mechanically skinned after observation of DTT-induced contraction. The skinned fiber contracted in response to a DTT concentration similar to that required to produce contraction in intact fibers before skinning. 5. In skinned fibers, DTT, at 100 or 200 mM, inhibited the accumulation of Ca2+ by SR, but not Ca2+ ATPase activity. 6. These results suggest that a high concentration of DTT triggers Ca2+ efflux from the SR through action on the Ca2+ release channel and/or closely associated proteins, such as triadin and FK-506 binding protein.
