Effects of ryanodine on skinned skeletal muscle fibers of the rabbit.
The mechanism(s) of ryanodine-induced contracture of skeletal muscle were studied in skinned fibers from soleus (SL) and adductor magnus (AM) (slow- and fast-twitch skeletal muscles) of rabbits. Pieces of SL or AM were homogenized (sarcolemma disrupted). Single fibers were dissected from the homogenate and mounted on photodiode force transducers. At concentrations 1-50 microM, ryanodine slightly but significantly increased the submaximal Ca2+-activated tension development of the contractile proteins in skinned fibers of AM but not of SL. Ryanodine in uptake phase or release phase increased caffeine-induced tension transients in the SR of both muscle types; however, no dose-response relation was found. Ryanodine greater than or equal to 1 microM decreased, however, the second control tension transients in a dose-dependent manner. The depression was nearly irreversible and "activity"-dependent. The concentrations of ryanodine that inhibited the second control tension transients by 50% were 10 microM and 5 microM for SL and AM, respectively, following ryanodine administration in the release phase, and 100 microM and 30 microM, respectively, for these preparations after the drug was present in the uptake phase. The quantity of calcium released from the SR by Triton X-100 and caffeine in the second control tension transient was unchanged by ryanodine at all concentrations tested when compared with that of the absence of ryanodine. The present findings suggest that the ability of ryanodine to increase immediate calcium release from the SR, and in AM but not SL, to increase the sensitivity of the contractile proteins to Ca2+ underlies the contracture caused by this agent in intact skeletal muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Anesthesiology, University of Washington School of Medicine, Seattle 98195.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects* / Q000648:ultrastructure; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism
D000470:Alkaloids; D012433:Ryanodine; D002118:Calcium