Role In Cell Volume Regulation Research Articles

Eicosanoids in renal function

The major role of renal eicosanoid synthesis appears to be a protective one. In the cortex, prostaglandin synthesis minimises potential anoxic and ischaemic damage by vasodilatation. In the medulla, prostaglandin synthesis appears to stabilise the corticomedullary solute gradient and may play a role in cell volume regulation. Mono-oxygenase production at this site, by modifying blood flow and cellular active transport processes could again serve a protective function against anoxia and ischaemia. The release of erythropoietin also appears to be prostaglandin dependent. It is likely that leukotrienes released from inflammatory cells within the kidney will affect renal haemodynamics and capillary permeability as in other tissues.

Ionic dependence of the extracellular ATP‐induced permeabilization of transformed mouse fibroblasts: Role of plasma membrane activities that regulate cell volume

Extracellular ATP rendered the plasma membrane of transformed mouse fibroblasts permeable to normally impermeant molecules. This permeability change was prevented by increasing the ionic strength of the isotonic medium with NaCl. Conversely, the cells exhibited increased sensitivity to ATP when the NaCl concentration was decreased below isotonicity, when the KCl concentration was increased above 5 mM while maintaining isotonicity, and when the pH of the medium was raised above 7.0. These conditions as well as the addition of ATP itself caused cell swelling. However, the effect of ATP was independent of cell volume and dependent upon the ionic strength and not the osmolarity of the medium since 1) addition of sucrose to isotonic medium did not prevent permeabilization although media made hypertonic with either sucrose or NaCl caused a decrease in cell volume; and 2) addition of sucrose or NaCl to hypotonic media caused a decrease in cell volume, but only NaCl addition decreased the response to ATP. Conditions that have been shown to inhibit plasma membrane proteins that play a reciprocal role in cell volume regulation had reciprocal effects on the permeabilization process, even though the effect of ATP was independent of cell volume. For example, inhibition of the Na+,K+-ATPase by ouabain increased sensitivity of cells to ATP while conditions which inhibit Na+,K+,Cl- -cotransporter activity, such as treatment of the cells with the diuretics furosemide or bumetanide or replacement of sodium chloride in the medium with sodium nitrate or thiocyanate, inhibited permeabilization. The furosemide concentration that inhibited permeabilization was greater than the concentration that inhibited Na+,K+,Cl- -cotransporter-mediated 86Rb+ (K+) uptake, suggesting that the effect of furosemide on the permeabilization process may not be specific for the Na+,K+,Cl- -cotransporter.

Volume-sensitive taurine transport in fish erythrocytes.

Taurine plays an important role in cell volume regulation in both vertebrates and invertebrates. Erythrocytes from two euryhaline fish species, the eel (Anguilla japonica) and the starry flounder (Platichthys stellatus) were found to contain high intracellular concentrations of this amino acid (approximately equal to 30 mmol per liter of cell water). Kinetic studies established that the cells possessed a saturable high-affinity Na+-dependent beta-amino-acid transport system which also required Cl- for activity (apparent Km (taurine) 75 and 80 microM; Vmax 0.85 and 0.29 mumol/g Hb per hr for eel (20 degrees C) and flounder cells (10 degrees C), respectively. This beta-system operated with an apparent Na+/Cl-/taurine coupling ratio of 2:1:1. A reduction in extracellular osmolarity, leading to an increase in cell volume, reversibly decreased the activity of the transporter. In contrast, low medium osmolarity stimulated the activity of a Na+-independent nonsaturable transport route selective for taurine, gamma-amino-n-butyric acid and small neutral amino acids, producing a net efflux of taurine from the cells. Neither component of taurine transport was detected in human erythrocytes. It is suggested that these functionally distinct transport routes participate in the osmotic regulation of intracellular taurine levels and hence contribute to the homeostatic regulation of cell volume. Volume-induced increases in Na+-independent taurine transport activity were suppressed by noradrenaline and 8-bromoadenosine-3', 5'-cyclic monophosphate, but unaffected by the anticalmodulin drug, pimozide.

Anion transport systems in the plasma membrane of vertebrate cells

In the case of the red blood cell, anion transport is a highly specific one-for-one exchange catalyzed by a major membrane protein known as band 3 or as capnophorin. This red cell anion-exchange system mediates the Cl-(-)HCO3- exchange responsible for most of the bicarbonate transport capacity of the blood. The rapidly expanding knowledge of the molecular biology and the transport kinetics of this specialized transport system is very briefly reviewed in Section III. Exchange diffusion mechanisms for anions are found in many cells other than erythrocytes. The exchange diffusion system in Ehrlich cells has several similarities to that in red cells. In several cell types (subsection IV-B), there is evidence that intracellular pH regulation depends on Cl-(-)HCO3- exchange processes. Anion exchange in other single cells is described in Section IV, and its role in pH regulation is described in Section VII. Anion exchange mechanism operating in parallel with, and only functionally linked to Na+-H+ or K+-H+ exchange mechanisms can also play a role in cell volume regulation as described in Section VII. In the Ehrlich ascites cell and other vertebrate cells, electroneutral anion transfer has been found to occur also by a cotransport system for cations and chloride operating in parallel with the exchange diffusion system. The cotransport system is capable of mediating secondary active chloride influx. In avian red cells, the cotransport system has been shown to be activated by adrenergic agonists and by cyclic AMP, suggesting that the cotransport is involved in regulatory processes (see subsection V-A.). In several cell types, cotransport systems are activated and play a role during volume regulation, as described in Section V and in Section VII. It is also likely that this secondary active cotransport of chloride plays a significant role for the apparently active extrusion of acid equivalents from certain cells. If a continuous influx of chloride against an electrochemical gradient is maintained by a cotransport system, the chloride disequilibrium can drive an influx of bicarbonate through the anion exchange mechanism, as described in Section VII. Finally, even the electrodiffusion of anions is shown to be regulated, and in Ehrlich cells and human lymphocytes an activation of the anion diffusion pathway plays a major role in cell volume regulation as described in Section VI and subsection VII-B.(ABSTRACT TRUNCATED AT 250 WORDS)

A tubulo-cisternal endoplasmic reticulum system in the potassium transporting marginal cells of the stria vascularis and effects of the ototoxic diuretic ethacrynic acid.

Sections of metal impregnated tissue and freeze-fracture have been used to examine intracellular membrane systems in marginal cells of the stria vascularis in mammalian cochleae. A continuous network of elements of the smooth endoplasmic reticulum was revealed. Notable features of this system were a series of flattened cisternae just inside and parallel with the lateral plasma membrane in continuity with an apical network of tubules, cisternae and sheets oriented in parallel with the luminal membrane. The whole system was closely associated with mitochondria. These characteristics suggest that the potassium transporting marginal cells possess a tubulo-cisternal endoplasmic reticulum (TER) like that found in many sodium transporting epithelial cells. The lateral elements of the TER dilated, appearing like vacuoles, and opened to the lateral extracellular space in response to the effects of ethacrynic acid. This diuretic impairs ion transport in the stria vascularis. It is suggested that the TER in marginal cells is involved in the transport of ions and fluid from the cell to the intercellular space when ion balance is disturbed and may play a role in cell volume regulation.

Proton motive force across the membrane of Mycoplasma gallisepticum and its possible role in cell volume regulation.

A proton motive force (delta (-) microH+) of 70 to 130 mV was measured across the membrane of Mycoplasma gallisepticum cells. The membrane potential was measured utilizing the lipid-soluble cation tetraphenylphosphonium. The method was validated by showing that in the presence of valinomycin the ratio of the concentrations (in/out) of tetraphenylphosphonium agreed well with those for K+ and Rb+. The pH gradient was calculated from the measured distribution ratio of benzoic acid. The proton motive force was approximately the same in cells harvested at early exponential, midexponential, and stationary phases of growth. The proportion of pH gradient to membrane potential varied with external pH. In the absence of glucose, cells incubated in an isosmotic NaCl solution showed low adenosine triphosphate and delta (-) microH+ levels and a tendency to swell and lyse compared with cells incubated with added glucose. It is concluded that energy is required for normal cell volume regulation.

Acclimation to successive short term salinity changes by the bivalve Modiolus demissus. II. Nitrogen metabolism

AbstractThe bivalve Modiolus demissus acclimates rapidly to new salinity regimes when exposed to successive short term osmotic stress. During exposure to hypoosmotic stress ventricular primary amine concentration decreases to an apparent steady‐state level within six hours, while hemolymph primary amine concentration increases. Upon re‐exposure to 100% sea water following a 6‐hour hypoosmotic stress, intracellular primary amines increase rapidly and return to control levels after six hours of exposure. Concomitant with this is an apparent decrease in hemolymph primary amine concentration. The rapidity with which reacclimation to hyperosmotic media proceeds and the pattern of change of individual amino acids suggests that transport of hemolymph FAA may play an important role in cell volume regulation induced by increases in external salinity.