Modulation of the ryanodine receptor sarcoplasmic reticular Ca2+ channel in skinned fibers of fast- and slow-twitch skeletal muscles from rabbits.
This study was performed to compare skinned fibers from rabbit adductor magnus (AM) and soleus (SL) muscles with regard to the influence of caffeine, Ca2+ and Mg2+ on the depressive effects of ryanodine (RYA) on the caffeine-induced tension transients. Single skinned fibers were immersed in solutions to load Ca2+ into, and release Ca2+ from the SR (a load-release cycle). Three cycles were sequentially performed in each skinned fiber: (1) a control (no RYA), (2) a conditioning period in which activation was carried out in the presence of ryanodine plus various concentrations of the modulators, i.e. caffeine, Ca2+ or Mg2+, and (3) a test (no RYA) which monitored the release activity retained after the conditioning cycle. The depressive effect of RYA was found to be a function of [ryanodine], [caffeine], or [Ca2+], and an inverse function of [Mg2+], where [] denotes concentration. The half-maximal effects of RYA in AM (5 microM RYA) and SL (10 microM RYA), respectively, occurred at a pCa50 of 5.32 versus 5.43 without caffeine, or pCa50 of 7.24 versus 6.88 and pMg50 of 3.29 versus 3.61 with 25 mM caffeine, at a [caffeine] of 4.96 versus 7.29 mM, and at a [ryanodine] of 31.0 versus 101.6 microM. Thus, the RYA depression in skinned muscle fibers is modulated by caffeine, Ca2+, and Mg2+ in both muscle types, and AM is at least two- to fourfold more sensitive than SL.
D000818:Animals; D002110:Caffeine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
D015220:Calcium Channels; D000697:Central Nervous System Stimulants; D002614:Chelating Agents; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002110:Caffeine; D004533:Egtazic Acid; D008274:Magnesium