ION GRADIENTS AND METABOLIC ENERGY IN ANIMAL TISSUE

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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 Expt Stud 1994;18:1040-56). We have completed a study of the effects of ethanol-induced change in hepatic voltage upon the gradients of all the amino acids between portal vein blood and liver and the gradients of the 9 major inorganic ions between intracellular and extracellular space in rat liver in vivo. To our knowledge, this is the first such study. Our work is also the first to show that the end product of hepatic ethanol metabolism, acetate, completely blocks the gut uptake of l-glutamine. l-Glutamine had been thought to be essential not only for its function as a building block for proteins, but also for its action as a bacterial barrier. The implication of the ability of acetate to inhibit the gut utilization of l-glutamine remains to be determined. 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.