Cell Membrane Changes

Figure 7.17 The potential across the axon-cell membrane changes in response to a stimulus, causing the potential to increase from its rest potential to its action potential...

Doxorubicin and dannorabicin are antibiotics made from microorganisms of the family Streptomyces peucetius. The stmcture of these anthracyclines contains an aminosaccarhide residue daunozamine attached to a naphthacenequinone nucleus. Doxorubicin differs from daunorubicin in the presence of a hydroxyl gronp at C14. A nnmber of mechanisms have been suggested in which anthracyclines exhibit cytotoxicity. They canse DNA to denature, are involved in oxidation-rednction reactions, chelate bivalent cations and react with cell membranes, changing their fnnction. They are used for severe leukemia, lymphoma, breast and ovarian cancer, and other solid tumors. 

Doxorubicin binds readily to cell membranes, changing their structure and function. The targets of doxorubicin binding are compounds with a negative charge, of which the most extensively studied is the phospholipid cardiolipin (Pollakis et al., 1983). Cardiolipin occurs in high concentrations in the inner mitochondrial membrane, where it is required for full activity of cytochrome c oxidase. In a recent study (Das and Mazumdar, 2000), the interaction between cytochrome c oxidase and cardiolipin in the presence of doxorubicin was analysed, and the results of pico-second time-resolved fluorescence depolarization showed that the cardiolipin layer was depleted due to complexation with the drug. 

Dugan, L.L. and Choi, D.W., 1994. Excitotoxicity, free radicals, and cell membrane changes, Ann. Neurol., 35, S17-S21. 

Apoptosis Caspase activation Cell membrane changes Changes of caspase activity DNA... 

Experiments with secondary monolayer cultures of human fetal astrxjcytes demonstrated that the addition of 0.01 mM MMC caused rapid retraction and coagulative cell membrane changes... 

Methods of isolating intact sarcolemma free from admixture with other cell structures are necessary for precise study of its chemical and enzymic composition and for the investigation of possible changes in these in disease. A number of procedures have been devised to this end [97, 98], but it appears that there are difficulties still to be overcome. The sarcolemma may be expected to be rich in phospholipids which are important constituents of cell membranes. Changes have been reported in the fatty acid composition of phospholipids in muscle in human muscular dystrophy [99], in the autosomal dominant form of myotonia congenita [100], after denervation [101], and in muscular dystrophy in the mouse [102, 103]. Further work will be required to show whether the phospholipids of the sarcolemma are concerned in these abnormalities. The increased turnover of proteolipids [104] and increased biosynthesis of gangliosides [105] in denervated muscle may also represent changes in the characteristics of the sarcolemma. 

M.p. 103°C. Noradrenaline is released in the adrenal medulla with adrenaline, and also at the sympathetic nerve endings. Its release from a nerve fibre is followed by binding to a receptor molecule on the next nerve or muscle fibre, probably causing a change in the electrical charge of the receptor-cell membrane. Biosynthetically it normally serves as a precursor for adrenaline. 

Cell Activation. Several studies have shown that platelets and white cells undergo shape changes when adhering to filter media. The cells are activated by contact with the filter media and form pseudopods which attach to the filter media. The cells membranes may need a certain degree of viabihty to be able to actively attach to the filter media. When white cells are treated with metaboHc inhibitors, the capabiUty of leukocyte reduction by the filter is reduced. 

The primary site of action is postulated to be the Hpid matrix of cell membranes. The Hpid properties which are said to be altered vary from theory to theory and include enhancing membrane fluidity volume expansion melting of gel phases increasing membrane thickness, surface tension, and lateral surface pressure and encouraging the formation of polar dislocations (10,11). Most theories postulate that changes in the Hpids influence the activities of cmcial membrane proteins such as ion channels. The Hpid theories suffer from an important drawback at clinically used concentrations, the effects of inhalational anesthetics on Hpid bilayers are very small and essentially undetectable (6,12,13). 

The aperture impedance principle of blood cell counting and sizing, also called the Coulter principle (5), exploits the high electrical resistivity of blood cell membranes. Red blood cells, white blood cells, and blood platelets can all be counted. In the aperture impedance method, blood cells are first diluted and suspended ia an electrolytic medium, then drawn through a narrow orifice (aperture) separating two electrodes (Fig. 1). In the simplest form of the method, a d-c current flows between the electrodes, which are held at different electrical potentials. The resistive cells reduce the current as the cells pass through the aperture, and the current drop is sensed as a change in the aperture resistance. 

In the first two cases, the permeability of the cell membrane to L-glutamate is altered through changes in the fatty add composition of the cell membrane. In the third case, the degradation of the amino add is inhibited, resulting in accumulation. 

The net electrochemical driving force is determined by two factors, the electrical potential difference across the cell membrane and the concentration gradient of the permeant ion across the membrane. Changing either one can change the net driving force. The membrane potential of a cell is defined as the inside potential minus the outside, i.e. the potential difference across the cell membrane. It results from the separation of charge across the cell membrane. 

Some drains act on the body by changing the cellular environment, either physically or chemically. Physical changes in the cellular environment include changes in osmotic pressures, lubrication, absorption, or the conditions on the surface of the cell membrane An example of a drag that changes osmotic pressure is mannitol, which produces a change in the osmotic pressure in brain cells, causing a reduction in cerebral edema A... 

The macrolides are bacteriostatic or bactericidal in susceptible bacteria The drugs act by binding to cell membranes and causing changes in protein function. 

Measurements of metabolite concentrations in muscle fibers before and after fatiguing stimulation have shown that ATP decreases from 6 to 4.6 mM and PCr decreases from 35 to 2.4 mM with a calculated increase in Pj from 3 to 38 mM (Dawson et al., 1978 Nassar-Gentina et al., 1978). The free ADP concentration was calculated to increase from 30 to 200 pM. At the same time pH decreased from 7.0 to 6.5 (Dawson et al., 1978 Juel, 1988 Westerblad and Lannergren, 1988). The effect of these metabolic changes has been studied in skinned muscle fibers, i.e., fibers in which the cell membrane has been removed. The skinning of the fibers... 

Fluorescein absorbance is sensitive to pH. This property is utilized to measure cytosolic pH changes. Fluorescein derivatives that contain esters on the carboxyl groups have been constructed. These compounds partition through the cell membrane and, once inside the cell, the esters are cleaved by nonspecific esterases in the cytosol, leaving free carboxyl groups thus the probe cannot diffuse out of the cell (or at least does so slowly). Commonly used derivatives are 6-carboxyfluorescein (21-23) and the more recently developed probe 2, 7 -bis(2-carboxyethyl)-5(and-6)-carboxyfluorescein (13, 24,25). 

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