Changes in cation transport during affective illness: Do they have therapeutic implications?

Abstract

Changes in some of the specific mechanisms which transport cations across cell membranes have been demonstrated in patients suffering from affective illness. A number of novel strategies have been evaluated in the management of both mania and depression, based on the following observations: (1) State-related changes in cation transport; (2) The effects of established psychotherapeutic drugs upon cation transport; and (3) theories regarding control of membrane ion flux. This article reviews the background to these novel strategies and evaluates the possible significance of changes in a number of different cation transport systems to the treatment of the affective disorders.KEY worms-Cation transport, affective illness, vanadium, Na+, K+-ATPase neurotransmitters CATION TRANSPORT There is a difference between the prevailing concentrations of sodium and potassium on the two sides of cell membranes. The concentration of potassium inside the cell is high relative to the extracellular fluid, the gradient of sodium concentration being in the opposite direction (extracellular > intracellular). The concentration gradients are important to many aspects of cellular function and, in particular, are the basis of the potential difference that exists across the cell membrane. Each cation tends to 'leak' across the membrane down its own concentration gradient and active processes are necessary to pump ions back against the gradient in order that these concentration differences be maintained. The mechanisms of cation transportThere are three different groups of transport systems which facilitate the movement of cations across cell membranes (see Figure 1).(1) One group of systems are energy-dependent ion 'pumps'. These are complex enzymes, often made up of several subunits, which move one or more ions across the membrane, up a concentration gradient. The energy for this process comes from the linked hydrolysis of the high-energy bond of adenosine triphosphate (ATP)-the major store for cellular energy. These enzymes are known collectively as the ATPases. The best-characterized of these systems is the sodium-and potassiumdependent adenosinetriphosphatase (Na+, K+-ATPase), also known as the sodium pump.Another group of transport mechanisms link one energy-producing cation movement to a second energy-requiring cation shift. The best example of such a system is the Na+/K+ co-transport system which links the inward (extracellular fluid to cytoplasm) flux of sodium ions, down the sodium concentration gradient , to the energy-requiring process of inward movement of potassium ions up the potassium concentration gradient. The energy for this process comes initially from the maintenance of the sodium gradient by the sodium pump. There are also a number of channels spanning the membrane which facilitate the transport of particular ions. They can be controlled (opened or closed) either by changes in the potential difference across the membrane, by changes in the concentration of other ions, and by a number of drugs, hormones and other messenge...

Involvement of Sulfhydryl Groups in the Transport of <i>L</i>-Tyrosine and <i>L</i>-Tryptophan across the Human Red Cell Membrane in vitro

“…On the other hand, electrolytes such as sodium, lithium and potassium seem to be implicated also in affective disorders [Rybakowski et al, 1986;Wood, 1987], Recently, a decrease in sodium intracellu lar concentration and an increase in potassium were observed in such patients [Joffe et al, 1986], We de scribed in healthy subjects the influence on the transport of the two neutral amino acids by countertransport (Na+-Li+ phloretin-sensitive) and by other electrolyte move ments , In order to investigate further the mechanism of this transport and to identify the extent of the perturbation on the psychiatric condition, we decided to test the role played by sulfhydryl groups (SH). These thiol groups (cysteine residues) are essential in maintaining the struc tural integrity and function of the red cell membrane [Deuticke, 1986].…”

Weak Association between Blood Sodium, Potassium, and Calcium and Intensity of Symptoms in Major Depressed Patients

“…None of these biochemical indices were related to anxiety, closely related to the intensity of depression, as recently confirmed [33]. Ab normalities in peripheral electrolyte transport, such as active sodium and calcium transport across the cells (erythrocytes in this case) as observed, should not be directly followed by extra-or intracellular electrolyte per turbations [34], For example, a decrease in active sodium transport, out of the cell, resulting in a strong increase in intracellular sodium content, may be quickly followed by an increase in other transport mechanisms (sodium/ potassium symport; sodium/proton exchange) to main tain adequate blood electrolyte homeostasis. In conclu sion, there was no evident association between plasma and erythrocyte sodium and potassium and between plas ma calcium in major depressed patients separated accord ing to gender, intensity of anxiety, psychomotor retarda tion and moral distress.…”

The Biology of Manic Depressive Illness (The Ole Rafaelsen Memorial Lecture)

“…These abnormalities are state dependent, and become normal after clinical recovery. These changes could be related to a reduction in sodiudpotassium ATPase activity during mood disorders and a change in activity on recovery (6). This has been demonstrated in the erythrocyte membranes in patients following recovery…”