Lithium cell membranes

Ce +. 35 341-342, 356-357 Cell membranes, lithium, 36 58-61 Cellulose decomposition, 46 316-317 Cerium... 

Most human cells are exposed to less than 2 mM Li+, and in most tissues the intracellular Li+ concentration is lower than the extracellular concentration. The level inside cells is generally below that expected for the passive diffusion of the Li+ ion across the cell membrane, indicating that Li+ is actively transported out of cells. For instance, the concentration of Li+ inside the erythrocytes from people taking lithium salts is low with a typical ratio of intra- to extracellular Li+ of 0.5 [53]. 

As lithium is an alkaline earth metal which readily exchanges with sodium and potassium, it is actively transported across cell membranes. The penetration of kidney cells is particularly rapid, while that of bone, liver and brain tissue is much slower. The plasma CSE ratio in man has been calculated to be between 2 1 and 3 1, which is similar to that found for the plasma red blood cell (RBC) ratio. This suggests that the plasma RBC ratio might be a useful index of the brain concentration and may be predictive of the onset of side effects, as these appear to correlate well with the intracellular concentration of the drug. 

Lithium has numerous pharmacologic effects. It is able to cross through sodium channels, competing with monovalent and divalent cations in cell membranes (AHFS, 2000). Animal studies have shown that lithium at a serum level of 0.66 + — 0.08 mEq/L can increase the amphetamine-induced release of serotonin (5-hydroxytryptamine [5-HT]) and the concentrations of a serotonin metabolite (e.g., 5-hydroxyindoleacetic acid [5-HIAA]) in the perifornical hypothalamus (PFH) of rats before and after chronic lithium chloride administration (Baptista et ah, 1990), a mechanism possibly involved in lithium s antidepressant effect. The precise neurobiological mechanisms through which lithium reduces acute mania and protects against recurrence of illness remain uncertain (Lenox and Hahn,... 

Mallinger AG, Hanin 1, Himmeloch JM, et al Stimulation of cell membrane sodium transport activity by lithium possible relationship to therapeutic action. Psychiatry Res 22 49-59, 1987... 

Dorus E, Pandey GN, Shaughnessy R, et al. Lithium transport across red blood cell membrane a cell membrane abnormality in manic-depressive illness. Science 1979 205 932-934. 

CCAs (channel blockers influx inhibitors) have been used primarily for the treatment of cardiovascular disorders (e.g., supraventricular arrhythmias, angina, and hypertension). Agents such as verapamil exert their effects by modulating the influx of Ca across the cell membrane, thus interfering with calcium-dependent functions. Based partly on the common effects of lithium and this class of drugs (e.g., effects on Ca "" activity), the CCAs have been studied as a potential treatment for mania. Janicak et al. (251) reported the results of a 3-week, double-blind comparison of verapamil versus placebo, which did not demonstrate a beneficial effect for verapamil (up to 480 mg/day) in 33 acutely manic hospitalized patients. 

Figure 13.27. Selectivity of the Sodium Channel. The ionic selectivity of the sodium channel partly depends on steric factors. Sodium and lithium ions, together with a water molecule, fit in the channel, as do hydroxylamine and hydrazine. In contrast, K+ with a water molecule is too large. [After R. D. Keynes. Ion channels in the nerve-cell membrane. Copyright 1979 by Scientific American, Inc. All rights reserved.]...

The Affective Disorders Manic Depressive Psychoses Lithium in the Affective Disorders A. Side Effects Chemistry Isotopes of Lithium Inorganic Biochemistry Mechanisms of Action Lithium and the Phosphoinositide Signaling System Lithium and the Cell Membrane A. Sodium-Lithium Exchange Anion Exchange Leak... 

In all these proposed mechanisms it is essential to prove that the relevant conditions exist in the cell during lithium therapy in patients. It is important to attempt to establish the extent to which lithium enters the cells, or perhaps becomes closely associated with cell membranes. Recent work using nuclear magnetic resonance suggests that lithium uptake into cells under conditions of acute exposure is relatively low (97-99). 

The most extensive studies for lithium transport across cell membranes have used erythrocytes because they are readily obtained and occur as individual cells freely floating in a suspending plasma medium. However, lithium uptake in these cells may not reflect uptake into other tissues due to their atypical morphology and metabolism. 

There may be abnormalities in eiythrocyte membrane transport properties in patients with bipolar affective disorders, though the interpretation is confounded by the uncertainty with regard to the contribution of hypertension in patients who are coincidentally hypertensive and manic depressive. The administration of lithium also may cause adaptive change (93,117,135-137). This results in an increase in erythrocyte lithium concentrations after prolonged lithium therapy, which could be mediated either by increased flux into the cell or via reduction in efflux rate. An increased content of ankyrins, red cell membrane proteins affecting cytoskeletal structure and functions, has been found in some patients with bipolar affective disorder (138) and this raises further the role of erythrocyte membrane defects in the etiology of the disease. 

A glance through the table of contents provides an overview of the issues commonly encountered by chemists in the automotive industry. The author discusses fuels cells, lithium ion batteries, carbon nanotubes, and nickel metal hydride technology, all of which requires the technical knowledge of a chemist but crosses the lines of various disciplines. He covers future technology including items such as battery technology, fuel cell membranes, and environmentally friendly plastics such as nylons that use castor oil as a primary component. 

Studies have also shown that lithium increases the uptake of norepinephrine and serotonin into neurons. It also reduces the release of norepinephrine from vesicles (packets of neurotransmitters inside neurons). These vesicles usually travel to the cell membrane and dump neurotransmitters into the synapse when a neuron is activated. Thus, overall, there is less neurotransmission in general. This effect of lithium has also been proposed as a way to alleviate the manic phase of bipolar disorder. 

Lithium is similar to sodium in that it forms positive ions (Li+) and can pass through sodium ion channels in neuronal cell membranes. It tends to accumulate inside neurons and may interfere with nerve action potentials or the activation of second messenger systems within the neuron (see Chapter 3, page 63). In addition, lithium may inhibit the release of monoamines from nerve endings and increase their uptake. However, the exact mode of action of lithium in affective disorders is unknown. 

Numerous investigations on the transport of the lithium ion through cell membranes of erythrocytes have established five different pathways by which anion exchange and sodium-potassium co-transport control lithium uptake into the cell, whilst... 

Oxygen gas is developed while the hydrogen is bound into the metal. A few tests were conducted with the lithium hybrid process, which has been developed at the RWTH Aachen, Germany. Out of some 40 candidate materials for the cell membrane, TiNi alloys were shown to be corrosion resistant for more than 500 h under electrolysis conditions. A thermodynamic analysis indicates an efficiency of 45 %, if hydrogen at a pressure of 4 MPa is provided [15],... 

A. Lithium is a cation that enters cells and substitutes for sodium or potassium. Lithium is thought to stabilize cell membranes. With excessive levels, it depresses neural excitation and synaptic transmission. 

In view of the influence of a complex matrix on the FD determination, e.g. in physiological fluids and tissues, and the importance of the use of lithium in medicine a further step was to exploit the utility of FDMS in combination w th signal accumulation and stable isotope dilution (internal standard) in this field. Lithium salts are used in the chemotherapy of manic-depressive psychoses . The transport phenomena of lithium through cell membranes and the mode of therapeutic action in elevated lithium levels are areas of biomedical research which are of special interest for the therapy of certain affective disorders. Concerning the accurate determination of very small lithium concentrations in the range of the normal physiological level, there is a special need for a reliable analytical technique, in particular, if only microliters of the sample are available. 

The authors attribute the bradycardia to an interaction with lithium as the low dose of propranolol was considered unlikely to cause bradycardia alone. They also point out that both drugs affect the movement of calcium across cell membranes, which could account for the decreased contraction rate of the heart muscle, and thus bradycardia in this patient. They suggest careful monitoring in elderly patients with atherosclerotic cardiovascular problems. ... 

Interest in the measurement of intracellular activities centres on transmembrane potentials and on the transport of ions across membranes. For example, lithium salts feature in the treatment of mania, but owing to the analytical problems little has been known of lithium accumulation or about its transport by nerve cell membranes. However, a recently developed microlithium electrode based on a liquid membrane sensor has established [280] an active transport of lithium ions out of Helix aspersa pallial ganglia and that at low external levels there is even less intracellular than extracellular lithium ions. It is therefore difficult to appreciate how lithium could function in an intracellular capacity to alter the neuronal properties in lithium psychiatric therapy [280]. 

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