Ion Gradients And Metabolic Energy In Animal Tissue

Veech, Richard

Abstract

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.