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Hyponatremia has complex pathophysiology, is frequent and has potentially severe clinical manifestations, and its treatment is associated with high risks. Hyponatremia can be hypertonic, isotonic or hypotonic. Hypotonic hyponatremia has multiple etiologies, but only two general mechanisms of development, defective water excretion, usually because of elevated serum vasopressin levels, or excessive fluid intake. The acute treatment of symptomatic hypotonic hyponatremia requires understanding of its targets and risks and requires continuous monitoring of the patient's clinical status and relevant serum biochemical values. The principles of fluid restriction, which is the mainstay of management of all types of hypotonic hyponatremia, should be clearly understood and followed. Treatment methods specific to various categories of hyponatremia are available. The indications and risks of these treatments should also be well understood. Rapid correction of chronic hypotonic hyponatremia may lead to osmotic demyelination syndrome, which has severe clinical manifestations, and may lead to permanent neurological disability or death. Prevention of this syndrome should be a prime concern of the treatment of hypotonic hyponatremia. [ABSTRACT FROM AUTHOR]

Abstract: Voltage-gated potassium channels (VGPCs) play an important role in many physiological functions by controlling the electrical properties and excitability of cells. Changes in tonicity in the peripheral nervous system can activate nociceptors and produce pain. Here, using whole cell patch clamp techniques, we explore how hypo- and hypertonicity modulate VGPCs in cultured rat and mouse trigeminal ganglion (TG) neurons. We found that hypo- and hypertonicity had different effects on slow-inactivating K+ current (I K) and fast-inactivating K+ current (I A): hypotonicity increased I K but had no effect on I A while hypertonicity depressed both I K and I A. The increase of I K by hypotonicity was mimicked by transient receptor potential vanilloid 4 (TRPV4) receptor activator 4α-phorbol-12,13-didecanoate (4α-PDD) but hypotonicity did not exhibit increase in TRPV4−/− mice TG neurons, suggesting that TRPV4 receptor was involved in hypotonicity-induced response. We also found that inactivation of PKC selectively reversed the increase of I K by hypotonicity, whereas antagonism of G-protein selectively rescued the inhibitions of I K and I A by hypertonicity, indicating that different intracellular signaling pathways were required for the modulation by hypo- and hypertonicity. In summary, changes in osmolality have various effects on I K and I A and different receptors and second messenger systems are selective for the modulation of VGPCs induced by hypo- versus hypertonicity. [Copyright &y& Elsevier]

The roles of various inorganic ions and taurine, an organic osmolyte, in cell volume regulation were investigated in the perfused liver of a freshwater air-breathing catfish Clarias batrachus under aniso-osmotic conditions. There was a transient increase and decrease of liver cell volume following hypotonic (-80 mOsmol/l) and hypertonic (+80 mOsmol/l) exposures, respectively, which gradually decreased/increased near to the control level due to release/ uptake of water within a period of 25-30 min. Liver volume decrease was accompanied by enhanced efflux of K+ (9.45 ± 0.54 µmol/g liver) due to activation of Ba2+- and quinidine-sensitive K+ channel, and to a lesser extent due to enhanced efflux of Cl- (4.35 ± 0.25 µmol/g liver) and Na+ (3.68 ± 0.37 µmol/g liver). Conversely, upon hypertonic exposure, there was amiloride- and ouabain-sensitive uptake of K+ (9.78 ± 0.65 µmol/g liver), and also Cl- (3.72 ± 0.25 µmol/g liver). The alkalization/acidification of the liver effluents under hypo-/hypertonicity was mainly due to movement of various ions during volume regulatory processes. Taurine, an important organic osmolyte, appears also to play a very important role in hepatocyte cell volume regulation in the walking catfish as evidenced by the fact that hypo- and hyper-osmolarity caused transient efflux (5.68 ± 0.38 µmol/g liver) and uptake (6.38 ± 0.45 µmol/g liver) of taurine, respectively. The taurine efflux was sensitive to 4,4′-di-isothiocyanatostilbene-2,2′-disulphonic acid (DIDS, an anion channel blocker), but the uptake was insensitive to DIDS, thus indicating that the release and uptake of taurine during volume regulatory processes are unidirectional. Although the liver of walking catfish possesses the RVD and RVI mechanisms, it is to be noted that liver cells remain partly swollen and shrunken during anisotonic exposures, thereby possibly causing various volume-sensitive metabolic changes in the liver as reported earlier. [ABSTRACT FROM AUTHOR]

SRC family kinases are a group of nine cytoplasmic protein tyrosine kinases essential for many cell functions. Some appear to be ubiquitously expressed, whereas others are highly tissue specific. The ability of members of the SRC family to influence ion transport has been recognized for several years. Mounting evidence suggests a broad role for SRC family kinases in the cell response to both hypertonic and hypotonic stress, and in the ensuing regulatory volume increase or decrease. In addition, members of this tyrosine kinase family participate in the mechanotransduction that accompanies cell membrane deformation. Finally, at least one SRC family member operates in concert with the p38 MAPK to regulate tonicity-dependent gene transcription. [ABSTRACT FROM AUTHOR]

TonEBP (NFAT5) is a newly identified member of the Rel family of transcriptional activators that include NF-κB and NFAT1 to NFAT4. Activated in response to hypertonicity, TonEBP stimulates transcription of transporters of organic osmolytes, certain cytokines, and a molecular chaperone. We provide biochemical data demonstrating that full-length TonEBP dimerizes via the C-terminus of the Rel-homology domain (CRHD). The two polyglutamine motifs were not involved. The dimerization was not affected by nucleocytoplasmic shifts in TonEBP in response to changes in ambient tonicity. Preventing the dimer formation by deleting the CRHD did not affect the nucleocytoplasmic shifts. On the other hand, deletion of the CRHD prevented DNA binding and eliminated the dominant negative activity of a C-terminal truncated TonEBP. Furthermore, phosphorylation was dramatically reduced especially in hypertonic conditions by deletion of the CRHD. We conclude that dimerization is required for proper phosphorylation of TonEBP as well as DNA binding. [Copyright &y& Elsevier]

The ability of early proximal tubule cells of the Necturus kidney to regulate volume was evaluated using light microscopy, video analysis and conventional microelectrodes. Necturus proximal tubule cells regulate volume in both hyper- and hyposmotic solutions. Volume regulation in hyperosmotic fluids is HCO3- dependent and is associated with a decrease in the relative K+ conductance of the basolateral cell membrane and a decrease in the resistance ratio, Ra/Rbl. Volume regulation in hyposmotic solutions is also dependent upon the presence of HCO3- but is also inhibited by 2 mM Ba2+ in the basolateral solution. Hyposmotic regulation is accompanied by an increase in the relative K+ conductance of the basolateral cell membrane and an increase in Ra/Rbl. Neither hypo- nor hyposmotic regulation have any affect on the depolarization of the basolateral cell membrane potential induced by HCO3- removal. We conclude that volume regulation in the early proximal tubule of the kidney involves both HCO3(-)-dependent transport systems and the baso-lateral K+ conductance. [ABSTRACT FROM AUTHOR]