Role of p38<sup>MAPK</sup> in Cell Volume Regulation of Perfused Rat Liver

The purpose of this study is to contribute to understanding the role of Na+-K+-ATPase and of ionic cotransporters in the regulation of cell volume, by employing a model that describes the rates of change of the intracellular concentrations of Na+, K+, and Cl−, of the cell volume, and of the membrane potential. In most previous models of dynamic cellular phenomena, Na+-K+-ATPase is incorporated via phenomenological formulations; the enzyme is incorporated here via an explicit kinetic scheme. Another feature of the present model is the capability to perform short-term cell volume regulation mediated by cotransporters of KCl and NaCl. The model is employed to perform numerical simulations for a “typical” nonpolarized animal cell. Basically, the results are consistent with the view that the Na+ pump mainly plays a long-term role in the maintenance of the electrochemical gradients of Na+ and K+ and that short-term cell volume regulation is achieved via passive transport, exemplified in this case by the cotransport of KCl and NaCl.

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Cell volume regulation by skate erythrocytes: role of potassium

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1990.258.5.r1217 ◽

1990 ◽

Vol 258 (5) ◽

pp. R1217-R1223 ◽

Cited By ~ 1

Author(s):

K. G. Dickman ◽

L. Goldstein

Keyword(s):

Cell Volume ◽

Phorbol Ester ◽

Volume Regulation ◽

Regulatory Volume Decrease ◽

Cell Volume Regulation ◽

Disulfonic Acid ◽

Ionophore A23187 ◽

K Uptake ◽

K Transport

The role of K transport during cell volume regulation in response to extracellular osmolality, protein kinase C activation, and cellular Ca was examined in skate (Raja erinacea) red blood cells (RBC). Reduction of medium osmolality from 960 to 660 mosmol/kgH2O had no effect on K uptake or efflux despite a 25% increase in cell volume. Further reduction to 460 mosmol/kgH2O caused K uptake to double and K efflux to triple resulting in net K loss. Net K efflux in 460 mosmol/kgH2O medium was correlated with the presence of a regulatory volume decrease, which was sensitive to the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and insensitive to chloride replacement. K-K exchange was absent in both isotonic and hypotonic media. Treatment with the Ca ionophore A23187 in the presence of Ca had no effect on either cell volume or K efflux in isotonic medium, indicating the absence of Ca-activated K transport. In contrast, phorbol ester treatment caused cell volume, Na content, and proton and K efflux to increase. Consistent with activation of Na-H exchange, phorbol ester effects were inhibited by dimethylamiloride. This study constitutes the first demonstration of volume-sensitive K transport in RBC from the most primitive vertebrate studied to date.

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Role of concentration and size of intracellular macromolecules in cell volume regulation

AJP Cell Physiology ◽

10.1152/ajpcell.1997.273.2.c360 ◽

1997 ◽

Vol 273 (2) ◽

pp. C360-C370 ◽

Cited By ~ 15

Author(s):

J. C. Summers ◽

L. Trais ◽

R. Lajvardi ◽

D. Hergan ◽

R. Buechler ◽

...

Keyword(s):

Cell Volume ◽

Volume Regulation ◽

Regulatory Volume Decrease ◽

Cell Volume Regulation ◽

Molecular Physiology ◽

Average Molecular Mass ◽

Membrane Stretch ◽

Ca2 Channels ◽

Volume Decrease

To gain insight into the mechanism(s) by which cells sense volume changes, specific predictions of the macromolecular crowding theory (A. P. Minton. In: Cellular and Molecular Physiology of Cell Volume Regulation, edited by K. Strange. Boca Raton, FL: CRC, 1994, p. 181-190. A. P. Minton, C. C. Colclasure, and J. C. Parker. Proc. Natl. Acad. Sci. USA 89: 10504-10506, 1992) were tested on the volume of internally perfused barnacle muscle cells. This preparation was chosen because it allows assessment of the effect on cell volume of changes in the intracellular macromolecular concentration and size while maintaining constant the ionic strength, membrane stretch, and osmolality. The predictions tested were that isotonic replacement of large macromolecules by smaller ones should induce volume decreases proportional to the initial macromolecular concentration and size as well as to the magnitude of the concentration reduction. The experimental results were consistent with these predictions: isotonic replacement of proteins or polymers with sucrose induced volume reductions, but this effect was only observed when the replacement was > or = 25% and the particular macromolecule had an average molecular mass of < or = 20 kDa and a concentration of at least 18 mg/ml. Volume reduction was effected by a mechanism identical with that of hypotonicity-induced regulatory volume decrease, namely, activation of verapamil-sensitive Ca2+ channels.

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Role of TASK2 Potassium Channels Regarding Volume Regulation in Primary Cultures of Mouse Proximal Tubules

The Journal of General Physiology ◽

10.1085/jgp.200308820 ◽

2003 ◽

Vol 122 (2) ◽

pp. 177-190 ◽

Cited By ~ 71

Author(s):

Herve Barriere ◽

Radia Belfodil ◽

Isabelle Rubera ◽

Michel Tauc ◽

Florian Lesage ◽

...

Keyword(s):

Cell Volume ◽

Volume Regulation ◽

Primary Cultures ◽

Regulatory Volume Decrease ◽

Cell Volume Regulation ◽

Proximal Tubules ◽

Wild Type ◽

Convoluted Tubules ◽

K Currents

Several papers reported the role of TASK2 channels in cell volume regulation and regulatory volume decrease (RVD). To check the possibility that the TASK2 channel modulates the RVD process in kidney, we performed primary cultures of proximal convoluted tubules (PCT) and distal convoluted tubules (DCT) from wild-type and TASK2 knockout (KO) mice. In KO mice, the TASK2 coding sequence was in part replaced by the lac-Z gene. This allows for the precise localization of TASK2 in kidney sections using β-galactosidase staining. TASK2 was only localized in PCT cells. K+ currents were analyzed by the whole-cell clamp technique with 125 mM K-gluconate in the pipette and 140 mM Na-gluconate in the bath. In PCT cells from wild-type mice, hypotonicity induced swelling-activated K+ currents insensitive to 1 mM tetraethylammonium, 10 nM charybdotoxin, and 10 μM 293B, but blocked by 500 μM quinidine and 10 μM clofilium. These currents were increased in alkaline pH and decreased in acidic pH. In PCT cells from TASK2 KO, swelling-activated K+ currents were completely impaired. In conclusion, the TASK2 channel is expressed in kidney proximal cells and could be the swelling-activated K+ channel responsible for the cell volume regulation process during osmolyte absorptions in the proximal tubules.

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