NACL TRANSPORT IN MEDULLARY THICK LIMB OF HENLE'S LOOP

肾脏粗大的Henle氏环升支(TALH)运输氯化物 积极对抗其电化学势梯度。它的运动是 哇巴因抑制利尿剂，如呋塞米和它的 运动似乎与钠在管腔内的运动有关。 通过钠-氯化物共转运系统的膜。虽然 氯化钠共转运系统已在 哺乳动物的小肠、胆管和气管上皮被 电生理测量，最近使用质膜的研究 小泡让人怀疑钠和钠的直接偶联是否 氯离子通量是否真的存在或是否通过Na/H和 发生了氯/羟基交换机制。因此，该项目建议 研究钠和氯化物在土壤中的转运机制 有髓之说。钠和氯化物进入的转运机制 将通过在隔离的Talh中进行通量研究来定义进入单元格 细胞和由这些细胞制备的腔质膜囊泡中。 这些研究将调查钠对氯化物的依赖 通量，反之，氯化物对钠通量的依赖可以是 演示了。这是证明一件事的基本标准 联运系统。氯化钠共转运的特性 系统将被研究，包括它在蜂窝中的定位 包膜、阴离子和阳离子的特异性，对多种敏感性 利尿剂和钾在共转运系统中的作用。这个 将研究共运输系统的化学计量学，以便 阐明管腔-正电位差的来源 存在于完整的小管中。此外，还计算了反应动力学参数。 将测量共传输系统，以便定量地定义 运输系统的分子特征。通过以下结果 本文对氯化钠的作用机理和生化性质进行了研究。 共转运系统，从而尿液浓缩的过程，将是 更好地理解。

The renal thick ascending limb of Henle's loop (TALH) transports chloride actively against its electrochemical potential gradient. Its movement is inhibited by ouabain, the 'loop' diuretics such as furosemide and its movement appears to be coupled to the movement of sodium across the luminal membrane via a sodium-chloride cotransport system. Although sodium-chloride cotransport systems have been extensively described in mammalian epithelia as the small intestine, gall bladder and trachea by electrophysiological measurements, recently studies using plasma membrane vesicles have cast doubt on whether a direct coupling of sodium and chloride fluxes really exists or whether a 'loose' coupling via Na/H and Cl/OH exchange mechanisms occurs. Thus, this project proposes to investigate the mechanisms of sodium and chloride transport in the medullary TALH. The transport mechanisms for sodium and chloride entry into the cell will be defined by conducting flux studies in isolated TALH cells and in luminal plasma membrane vesicles prepared from these cells. These studies will investigate whether a dependency of sodium on chloride fluxes and conversely a dependency of chloride on sodium fluxes can be demonstrated. This is an essential criterium for the proof of a cotransport system. The characteristics of the sodium-chloride cotransport system will be studied including its localization within the cellular envelope, the anion and cation specificity, the sensitivity to a variety of diuretics and the role of potassium in the cotransport system. The stoichiometry of the cotransport system will be studied in order to elucidate the origin of the lumen-positive potential difference which exists in the intact tubule. Additionally, the kinetic parameters of the cotransport system will be measured in order to define quantitatively the molecular characteristics of the transport system. Through the results of this study the mechanisms and biochemical properties of the sodium-chloride cotransport system, and thus the process of urinary concentration, will be better understood.