The action of ryanodine on force development of bundles dissected from rat extensor digitorum longus (EDL) and soleus muscles has been examined. 2. Ryanodine (100-5000 nM) irreversibly depressed twitch and tetanic tension of both muscle types in a dose-related manner. 3. At concentrations above 250 nM, ryanodine induced a slowly developing, dose-dependent contracture which could not be blocked by 5 mM-Co2+. Increasing the stimulation rate or decreasing the oxygenation of the preparation accelerated the rate of contracture development while the total removal of extracellular Ca2+ was required to prevent it. 4. Following the relaxation of the initial contracture (IC) in Ca2+-free solution, a second type of contracture (SC) could be induced by the readdition of Ca2+. This contracture differed from IC in that it was dependent on Ca2+ in the millimolar range and was prevented by 5 mM-Co2+. Both IC and SC were relaxed by perfusion with Ca2+-free, EGTA-containing solution. 5. Subcontracture doses of ryanodine (100 nM) markedly potentiated caffeine contractures of both muscle types. 6. Asymmetric charge movement in EDL fibres was recorded with the Vaseline-gap technique. The amount of charge moved near threshold was virtually unaffected by the presence of 10 microM-ryanodine over the time examined. 7. The results are consistent with the suggestion that ryanodine locks the calcium release channels of the sarcoplasmic reticulum (SR) in an open subconductance state with reduced conductance. It appears that lowering the external calcium concentration might still inactivate the release channels after they have been blocked open by ryanodine, possibly by an effect on the T-tubular voltage sensor.
摘要
研究了ryanodine对从大鼠趾长伸肌（EDL）和比目鱼肌分离出的肌束力量发展的作用。2. Ryanodine（100 - 5000 nM）以剂量相关的方式不可逆地降低了两种肌肉类型的单收缩和强直张力。3. 在浓度高于250 nM时，ryanodine诱导出一种缓慢发展的、剂量依赖性的挛缩，5 mM - Co2 +不能阻断这种挛缩。增加刺激频率或降低标本的氧合作用会加速挛缩的发展速度，而需要完全去除细胞外Ca2 +才能防止其发生。4. 在无Ca2 +溶液中初始挛缩（IC）松弛后，重新添加Ca2 +可诱导出第二种挛缩（SC）。这种挛缩与IC的不同之处在于它依赖于毫摩尔范围内的Ca2 +，并可被5 mM - Co2 +阻止。IC和SC通过用无Ca2 +、含EGTA的溶液灌注而松弛。5. 亚挛缩剂量的ryanodine（100 nM）显著增强了两种肌肉类型的咖啡因挛缩。6. 用凡士林间隙技术记录了EDL纤维中的不对称电荷移动。在检查的时间段内，10 microM - ryanodine的存在实际上未影响接近阈值时移动的电荷量。7. 结果与以下观点一致，即ryanodine将肌浆网（SR）的钙释放通道锁定在开放的亚电导状态，且电导降低。似乎在ryanodine将释放通道阻断打开后，降低细胞外钙浓度仍可能使释放通道失活，这可能是通过对T小管电压传感器的作用实现的。
