CHLORIDE TRANSPORT IN NERVE AND MUSCLE

将研究氯离子的跨膜转运，以进一步表征其 在两个不同的运输过程中发挥作用。在一种情况下，氯-是关键参与者 (与HCO3-、Na+和H+一起)在调节细胞内pH的过程中 (Phi)，这是细胞生理学中一个基本的重要功能。在 其他有待研究的转运过程是，氯与Na+和K+一起被吸收 进入了鱿鱼巨型轴突。这一过程可能与细胞体积有关 监管，另一项基本的细胞特性。实验是 提出确定ATP和Na+梯度的相对重要性 作为Phi调节系统和Cl-：Na+：K+的能源 摄取系统。有关PHI监管系统的其他研究包括 关心这个过程是如何被phi下降激活的，以及是否或 而不是Ca++在这一过程中起作用。Phi的当前型号 调控机制涉及一种外部膜介导的 外部Na+HCO3-为内部H+Cl-。当前的目标之一 建议对这一模型进行更详细的测试。Phi的调节是一种 相对较新的研究领域，对其仍有许多有待了解的地方 离子机制。乌贼体内的CL-Na~+：K~+摄取系统 巨型轴突与其他组织中描述的系统有一些相似之处， 尤其是在肾小管中。内透析的巨大轴突 为这方面的研究提供了独特而强大的实验优势。 运输系统。放射性同位素示踪剂与离子选择性微电极 将在这些研究中使用。鱿鱼巨型轴突和藤壶巨人 肌肉纤维将使用内透析技术(用于 两种准备方法)和内部灌流(藤壶巨肌纤维)。 之所以选择这些细胞，是因为它们的大小允许 使用内透析和灌流技术，使实验 细胞内环境的控制和细胞内环境的精确测量 单向通量和净通量。

Transmembrane transport of Cl- will be studied to further characterize its role in two separate transport processes. In one, Cl- is a key participant (along with HCO3-, Na+ and H+) in a process that regulates intracellular pH (pHi), a function of fundamental importance in cellular physiology. In the other transport process to be studied, Cl is taken up along with Na+ and K+ into the squid giant axon. This process may be involved in cellular volume regulation, another fundamental cellular property. Experiments are proposed to determine the relative importance of ATP and the Na+ gradient as an energy source for the pHi regulatory system and for the Cl-:Na+:K+ uptake system. Additional studies on the pHi regulatory system are concerned with how the process is activated by a fall of pHi and whether or not Ca++ plays a role in this process. The current model for the pHi regulatory mechanism involves an external membrane-mediated exchange of external Na+ HCO3- for internal H+ Cl-. One of the goals of the present proposal is to test this model in some detail. The regulation of pHi is a relatively recent field of study and much remains to be learned about its ionic mechanism. The CL-Na+:K+ uptake system now identified in the squid giant axon has some similarities to systems described in other tissues, especially in the kidney tubules. The internally dialyzed giant axon provides a unique and powerful experimental advantage for the study of this transport system. Radioisotopic tracers and ion-selective microelectrodes will be used in these studies. The squid giant axon and the barnacle giant muscle fiber will be studied using the techniques of internal dialysis (for both preparations) and internal perfusion (barnacle giant muscle fibers). These cells were chosen specifically because their large size permits the use internal dialysis and perfusion techniques which allow experimental control of the intracellular environment and the precise measurement of unidirectional and net fluxes.