CHLORIDE TRANSPORT IN NERVE AND MUSCLE

将研究Cl-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。 其中之一，Cl-是一个关键的参与者， （沿着HCO 3-、Na+和H+）在调节细胞内pH的过程中 (pHi)这是细胞生理学中的一个基本重要功能。 在 Cl与Na+、K+一起被沿着吸收 进入乌贼巨大的轴突。 这一过程可能涉及细胞体积 调节，另一个基本的细胞特性。 实验 建议确定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 关于pHi调节系统的其他研究包括： 关注的是这个过程是如何被pHi的下降激活的， 而不是Ca++在此过程中起作用。 当前的pHi模型 调节机制涉及外膜介导的 外部Na+ HCO 3-为内部H+ Cl-。 目前的目标之一是 建议是对这个模型进行详细的测试。 pHi的调节是 这是一个相对较新的研究领域，关于它的研究还有很多东西有待了解。 离子机理 CL-Na+：K+摄取系统现已在鱿鱼中鉴定 巨轴突与其他组织中描述的系统有一些相似之处， 尤其是肾小管 内部透析的巨大轴突 为研究这一问题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和离子选择性微电极 将用于这些研究。 乌贼的巨大轴突和藤壶巨人 肌纤维将使用内部透析技术进行研究（用于 两种制剂）和内部灌注（藤壶巨肌纤维）。 这些细胞是专门选择的，因为它们的大尺寸允许 使用内部透析和灌注技术， 细胞内环境的控制和精确测量 单向和净通量。

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.