Ion Gradients And Metabolic Energy In Animal Tissue

工作灌注心脏中9种主要无机离子的梯度能量、胞外期和胞内期电位和ATP水解DG之间的能量接近平衡（Masuda T et al, J Biol Chem 1990; 266:20321-34）。乙醇的代谢使肝细胞的静息电位从28 mV增加到40 mV （Veech RL et al ., Alcoholism clinical Exp, 1994;18:10 -56）。先前，我们发现仅仅改变可用的底物就能改变心脏中ATP水解的DG （Kashiwaya Y et al, Am J Cardiol 1997;80:50A- 64A）。由于任何类型的损伤都会引起细胞离子分布的刻板变化，其中细胞获得Na+，失去K+并膨胀，因此损伤的这些刻板变化可能通过简单地改变给予损伤或烧伤受害者的液体成分来逆转。根据这些研究和我们向医学学会召集的一个小组提出的建议，建议开始调查制造新的复苏液的可行性（见：《液体复苏》，治疗战斗伤亡和平民受伤的科学现状，国家科学院出版社，1999年）。目标是改善出血和烧伤的标准治疗，这在过去的50年里没有改变。我们正在与海军血液研究实验室合作。我们现在已经提交了关于ATP水解的δ G与心脏、肝脏和红细胞细胞外和细胞内所有9种常见无机离子梯度能量的关系。这些组织的电位从-86 mV到-28 mV到-6 mV不等。我们发现Na+梯度的能量约为ATP水解能量的1/3，并且通过KCl微电极测量的静息膜电位是电泳最渗透离子所需的功函数。因此，离子梯度系统似乎是一个依赖于ATP水解能量的吉布斯多南近平衡系统。这导致研制和测试了一系列新的肠外液体，用于军事和民用环境中的出血、复苏和烧伤治疗。

The energy of the gradients of the nine major inorganic ions in working perfused heart are in near equilibrium with each other, the electrical potential between extra- and intracellular phase and the DG of ATP hydrolysis (Masuda T et al, J Biol Chem 1990;265:20321-34). The metabolism of ethanol increases the resting electrical potential of hepatocytes from 28 to 40 mV (Veech RL et al, Alcoholism Clin Exp Res 1994;18:1040-56). Previously, we showed that merely changing the substrate available altered the DG of ATP hydrolysis in heart (Kashiwaya Y et al, Am J Cardiol 1997;80:50A- 64A). Since injuries of any sort induce a stereotypic change in cellular ionic distributions wherein the cell gains Na+, loses K+ and swells, these stereotypic changes of injury can possibly be reversed by simple changes in the compositions of fluids administered to victims of injury or burns. As a result of these studies and our suggestions to a panel convened by the Academy of Medicine, a recommendation has been made that investigation of the feasibility of making new resuscitation fluids be initiated (see: Fluid Resuscitation, state of the science for treating combat casualties and civilian injuries, National Academy Press, 1999). The goal is to improve the standard treatment of hemorrhage and burns, which has not changed over the past 50 years. We are collaborating in this effort with the Naval Blood Research Lab. We have now submitted for publication relating the Delta G of ATP hydrolysis to the energy of the gradients of all 9 common inorganic ions between extra and intracellular phases of heart, liver and red blood cell. These tissues differ in electrical potential from -86 to -28 to -6 mV. We found that the energy of the Na+ gradient was about 1/3 of the energy of ATP hydrolysis and that the resting membrane potential as measured by KCl microelectrodes was a work function required to electrophoresis the most permeant ion. The system of ion gradients therefore appears to be a Gibbs Donnan near-equilibrium system dependent upon the energy of ATP hydrolysis. This has led to the preparation and testing of a new family of parenteral fluids for use in hemorrhage, resuscitation and the treatment of burns in both military and civilian settings.