EXCITATION CONTRACTION COUPLING IN STRIATED MUSCLE

电压通过质膜发生变化的机制 横纹肌启动肌浆网钙释放 (Sr)是未知的，尽管多年来进行了广泛的实验。这 机制可以控制收缩，因此具有基础性和临床意义 意义。它也可能是控制钙的机制的类似物 在许多其他细胞中释放。讨论了耦合的几种机制。 并提出了一些实验，这些实验可能会排除一些，支持另一些。 许多拟议的实验利用了我们最近的发现，一种钙 进入阻滞剂D-600使单个骨骼肌纤维瘫痪，在 在寒冷中调节肌挛缩。这一发现将使我们能够研究 收缩与非线性电荷运动的关系(被认为是 电压和钙释放之间的重要联系)；它将允许研究 与收缩相关的放射性钙内流；它将允许 与收缩相关的假定钙电流流动的研究， 采用电压钳位法。初步工作表明，这些实验是 可行：没有非线性电荷运动， 放射性钙在瘫痪的纤维中被还原。实验是 提出了以生理揭示的方式改变收缩的方法； 其他实验的目的是为了阐明 D-600麻痹，到目前为止类似于局部麻醉剂的机制 对钠通道的作用由Hille的调制受体模型描述。 我们的初步结果与以下观点是一致的： 跨过T膜的电压变化和SR的钙释放是一个 通过血浆中特殊通道的信使钙的流动 三联体/二联体连接的膜。(结果与 其他机制也是如此，但似乎只有当D-600有不止一个 需要寒冷和先前的收缩的分子作用。)《信使》 机制需要细胞外钙流过血浆 膜，但已知骨骼肌在缺钙时收缩 解决方案，而心肌不。建议进行实验，以 解决缺钙行为之间的明显矛盾 一次近距离钙离子内流的解决方案和初步发现 与肌挛缩症有关。缺钙溶液的作用 将在钙泵不应 有效地维持细胞外钙的结合储存，即在 条件反射后的寒冷会导致痉挛。

The mechanism by which a voltage change across the plasma membranes of striated muscle initiates calcium release from the sarcoplasmic reticulum (SR) is not known, despite extensive experimentation for many years. This mechanism can control contraction and so is of fundamental and clinical significance. It may also be an analog of mechanisms controlling calcium release in many other cells. Several mechanisms of coupling are discussed and experiments are proposed which might rule out some and support others. Many of the proposed experiments exploit our recent finding that a calcium entry blocker D-600 paralyzes single skeletal muscle fibers, after a conditioning contracture in the cold. This finding will allow study of the relation of contraction and nonlinear charge movement (thought to be an essential link between voltage and calcium release); it will allow study of radioactive calcium influx associated with contraction; and it will allow study of the putative calcium current flow associated with contraction, using voltage clamp methods. Preliminary work shows these experiments are feasible: nonlinear charge movement is absent and the influx of radioactive calcium is reduced in paralyzed fibers. Experiments are proposed which may modify contraction in physiologically revealing ways; other experiments are designed to cast light on the molecular mechanism of D-600 paralysis, which so far resembles the mechanism of local anesthetic actions on sodium channels described by Hille's modulated receptor model. Our preliminary results are compatible with the idea that the link between voltage change across the T membrane and calcium release from the SR is a flux of messenger calcium through specialized channels in the plasma membrane of the triad/dyad junction. (The results are compatible with other mechanisms as well, but seemingly only if D-600 has more than one molecular action requiring the cold and prior contracture.) The messenger mechanism requires extracellular calcium to flow across the plasma membrane, yet skeletal muscle is known to contract in calcium deficient solutions whereas cardiac muscle does not. Experiments are proposed to resolve the apparent conflict between the actions of calcium deficient solutions and the preliminary finding of a calcium influx closely associated with contracture. The effects of calcium deficient solutions will be studied under conditions where a calcium pump should not be effective in maintaining a bound store of extracellular calcium, namely in the cold after conditioning contractures.