Activation of ion transport systems during cell volume regulation

Abstract

This review discusses the activation of transport pathways during volume regulation, including their characteristics, the possible biochemical pathways that may mediate the activation of transport pathways, and the relations between volume regulation and transepithelial transport in renal cells. Many cells regulate their volume when exposed to an anisotonic medium. The changes in cell volume are caused by activation of ion transport pathways, plus the accompanying osmotically driven water movement such that cell volume returns toward normal levels. The swelling of hypertonically shrunken cells is termed regulatory volume increase (RVI) and involves an influx of NaCl into the cell via either activation of Na-Cl, Na-K-2Cl cotransport systems, or Na+-H+ and Cl(-)-HCO3- exchangers. The reshrinking of hypotonically swollen cells is termed regulatory volume decrease (RVD) and involves an efflux of KCl and water from the cell by activation of either separate K+ and Cl-conductances, a K-Cl cotransport system, or parallel K+-H+ and Cl(-)-HCO3- exchangers. The biochemical mechanisms involved in the activation of transport systems are largely unknown, however, the phosphoinositide pathway may be implicated in RVI; phorbol esters, cGMP, and Ca2+ affect the process of volume regulation. Renal tubular cells, as well as the blood cells that traverse the medulla, are subjected to increasing osmotic gradients from the corticomedullary junction to the papillary tip, as well as changing interstitial and tubule fluid osmolarity, depending on the diuretic state of the animal. Medullary cells from the loop of Henle and the papilla can volume regulate by activating Na-K-2Cl cotransport or Na+-H+ and Cl(-)-HCO3- exchange systems. Both Na-Cl and Na-K-2Cl cotransport systems have been identified in the medullary Loop of Henle and it is postulated that the Na-K-2Cl cotransport system predominates during RVI and affects transepithelial NaCl transport while the Na-Cl cotransport system may function during RVD in these cells.

Taurine and Osmoregulation. III. Taurine Deficiency Protects against Cerebral Edema during Acute Hyponatremia

“…Quantitatively, inorganic ions constitute the bulk of the change in solute levels within cerebral cells during chronic hyper-and hyponatremia (23,24). A number of ion exchange mechanisms and selective conductive pathways are responsible for increases or decreases in the brain Na', K+, and C1-concentrations during osmolal stress states (25,26). In our experiments, reduced cerebral swelling seen in taurine-deficient cats cannot be attributed to a more pronounced adaptive decrease in brain inorganic ion content.…”

Mucociliary clearance during and after isocapnic hyperventilation with dry air in the presence of frusemide

“…The swelling of the hypertonically shrunken cells, termed regulatory volume increase (RVI), involves an influx of NaCl into the cell predominantly via the activation of Na + /K + /2Cl -co-transport system, which is activated by the cell shrinkage and inhibited by loop diuretics, such as frusemide and bumetanide [10,25,26]. The RVI can take up to 20 min to be complete [25,26].…”

“…Frusemide, a loop diuretic known to inhibit the Na + /K + /2Cl -and NaCl co-transport systems at the basolateral membrane [5], inhibits the airway narrowing induced by exercise [6], ISH [7,8], and hypertonic saline [9]. Inhibition of the co-transport systems affects the regulatory volume increase (RVI) of the hypertonically shrunken epithelial cells [10], and chloride secretion [5]. Therefore, frusemide has the potential to interfere with the water availability to the periciliary fluid layer.…”

Ca(2+)‐dependent heat production by rat skeletal muscle in hypertonic media depends on Na(+)‐Cl‐ co‐transport stimulation.

“…More recently, Na+-Cl-cotransport in soleus and extensor digitorum longus muscles from young rats has been associated with 86Rb+ influx (Dorup & Clausen, 1991). In the present study, the bumetanide-sensitive co-transport was simply referred to as a Na+-Cl-co-transport system because the need to distinguish between Na+-Cl-and Na+-K+-2Cl-cotransports (Eveloff & Warnock, 1987) was considered to be more circumstantial than real. The compensatory role of Na+Cl-co-transport stimulation in hyperosmotic environments, which limits cell volume loss, clearly illustrates this view.…”