CALCIUM MOVEMENTS IN EXCITATION-CONTRACTION COUPLING

动作电位到肌肉收缩的转导(EC偶联)是 细胞膜事件和代谢之间快速沟通的一个例子 州政府。正如在许多系统中一样，这种耦合的中心信使是 肌肉中的钙是从肌浆网(SR)释放出来的 来激活收缩蛋白。我们的目标是从数量上理解 这些钙离子的运动。 SR的释放通道受电位变化的控制 血浆和T管膜以一种不了解的方式，涉及一种 T管膜中的电压传感器和一种未知的机制 电压传感器和释放通道之间的通信(T-SR耦合)。 我们可以测量EC耦合步骤的主要变量：电荷 与电压传感器相关的运动电流，在 肌浆内[Ca]和钙通过释放通道的流量。横向的 肌管膜有一条(缓慢的)CA通道，这一通道尚不清楚 职能角色，数量很多。我们的结果表明，缓慢的情况下 通道与电荷运动和钙释放密切相关。我们计划 研究电荷运动，寻求其多描述的统一模型 组件以澄清其与CA版本的关系。我们将在 详细介绍慢钙通道和EC偶联事件的药理学 为了验证慢钙通道参与EC的假说 耦合。如果是这种情况，将寻求在T-SR耦合中的角色 钙通道和由该通道携带的电流。我们会研究 人工双层膜中慢钙通道的重组 在定义更好的离子条件下表征其性质。我们会 比较了三种提出的T-SR耦合机制的优点： 机械连接，钙，和IP3作为传递器。这将通过以下方式完成 在细胞内介质中引入选择性干扰的变化 通过建议的机制，包括快速钙缓冲器和阻滞剂 IP3代谢。 钙的释放、蛋白质和SR泵的清除是主要的 参与钙调节的通量。一种助熔剂的研究进展 生成并需要更多关于他人的知识。两国关系 在CA去除通量和由 将对肌肉进行研究。钙结合蛋白白蛋白将是 被引入肌肉纤维中，以测试其在内在信号和 在最终结束钙循环的清除过程中 动静。

The transduction of action potential to muscle contraction (EC coupling) is an example of fast communication between cell membrane events and metabolic state. As in many systems, the central messenger of this coupling is calcium, which in muscle is released from the Sarcoplasmic Reticulum (SR) to activate contractile proteins. Our goal is to understand quantitatively these Ca movements. The release channels of the SR are controlled by changes in potential at the plasma and T-tubular membrane in an ill-understood way, involving a voltage sensor in the T-tubular membrane and an unknown mechanism of communication between voltage sensor and release channel (T-SR coupling). We can measure the main variables of the EC coupling steps: charge movement currents associated to the voltage senor, the rapid change in myoplasmic [Ca] and Ca flux through the release channel. The transverse tubular membrane of muscle has a ('slow') CA channel, of no known functional role, in large numbers. Our results suggest that the slow Ca channel is intimately related to charge movement and Ca release. We plan to study charge movement, seeking a unified model of its many described componennts to clarify its relationship to CA release. We will compare in detail the pharmacology of the slow Ca channel and the EC coupling events to test the hypothesis that the slow Ca channel is involved in EC coupling. If this is the case a role in T-SR coupling will be sought for the Ca channel and the current carried by the channel. We will study the slow Ca channel reconsituted in artificial bilayer membranes to characterize its properties in better defined ionic conditions. We will compare the merits of three proposed mechanism of T-SR coupling: a mechanical link, calcium, and IP3 as a transmitter. This will be done by introducing changes in the intracellular medium that selectively interfere with the proposed mechanisms, including a fast Ca buffer and a blocker of IP3 metabolism. Release of Ca and its removal by proteins and the SR pump are the main fluxes involved in Ca regulation. Progress in the study of one flux generates and requires more knowledge about the other. The relationship between CA removal fluxes and an intrinsic optical signal generated by the muscle will be studied. The Ca binding protein pravalbumin will be introduced into muscle fibers to test its role in the intrinsic signal and in the process of removal that eventually closes the cycle of calcium movements.