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

Evidence suggests that ryanodien affects ligandgated 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>90% in papillary muscle (PM), 25% in soleus (SL), and 20% in adductor magnus (AM). Ryanodine (100 M for 1–3 s for AM and SL; 1 M 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 M) in the order of PM>AM>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>AM>PM. The data suggest that ryanodine affects Ca²⁺ releasing channel as a result of its binding to open channels.