Mechanisms of ryanodine-induced depression of caffeine-induced tension transients in skinned striated rabbit muscle fibers.

Evidence suggests that ryanodine affects ligand-gated calcium channels in the sarcoplasmic reticulum (SR) resulting in depressed muscle contraction. In skinned fibers from striated muscle the effects of ryanodine were examined (1) on Ca2+ uptake and on Ca2+ release to differentiate whether the effects are on the pump or channel, and (2) during the tension transient, with ryanodine exposure at various times either simultaneous with or directly after exposure to caffeine. Of total calcium content in the SR, 25 mM caffeine released greater than 90% in papillary muscle (PM), approximately equal to 25% in soleus (SL), and approximately equal to 20% in adductor magnus (AM). Ryanodine (100 microM for 1-3 s for AM and SL; 1 microM for 7-10 s for PM), in the initial loading phase, did not significantly change, and in the initial release phase, markedly depressed the subsequent control caffeine-induced tension transients (C2) in all three muscle types. The depression increased with increasing time of exposure to ryanodine (10 microM) in the order of PM greater than AM greater than SL. Upon introduction of ryanodine after caffeine-induced tension transients, maximal depression was observed at half-maximum rise of the tension transient, followed by recovery of depression to completion in SL, and only partially in AM and PM at steady state of relaxation. The extent of recovery was in the order of SL greater than AM greater than PM. The data suggest that ryanodine affects Ca2+ releasing channel as a result of its binding to open channels.