scholarly journals Coordinate modulation of Na-K-2Cl cotransport and K-Cl cotransport by cell volume and chloride

2002 ◽  
Vol 283 (5) ◽  
pp. C1422-C1431 ◽  
Author(s):  
Christian Lytle ◽  
Thomas McManus
Keyword(s):  
Cell Volume ◽  
Cell Volume Regulation ◽  
Specific Effect ◽  
Feedback System ◽  
Major Effect ◽  
Cell Swelling ◽  
Cell Shrinkage ◽  
Set Point

Na-K-2Cl cotransporter (NKCC) and K-Cl cotransporter (KCC) play key roles in cell volume regulation and epithelial Cl− transport. Reductions in either cell volume or cytosolic Cl− concentration ([Cl−]i) stimulate a corrective uptake of KCl and water via NKCC, whereas cell swelling triggers KCl loss via KCC. The dependence of these transporters on volume and [Cl−]i was evaluated in model duck red blood cells. Replacement of [Cl−]i with methanesulfonate elevated the volume set point at which NKCC activates and KCC inactivates. The set point was insensitive to cytosolic ionic strength. Reducing [Cl−]i at a constant driving force for inward NKCC and outward KCC caused the cells to adopt the new set point volume. Phosphopeptide maps of NKCC indicated that activation by cell shrinkage or low [Cl−]iis associated with phosphorylation of a similar constellation of Ser/Thr sites. Like shrinkage, reduction of [Cl−]i accelerated NKCC phosphorylation after abrupt inhibition of the deactivating phosphatase with calyculin A in vivo, whereas [Cl−] had no specific effect on dephosphorylation in vitro. Our results indicate that NKCC and KCC are reciprocally regulated by a negative feedback system dually modulated by cell volume and [Cl−]. The major effect of Cl− on NKCC is exerted through the volume-sensitive kinase that phosphorylates the transport protein.

Effect of hemorrhagic shock on hepatic transmembrane potentials and intracellular electrolytes, in vivo

1981 ◽  
Vol 240 (3) ◽  
pp. R211-R219 ◽  
Author(s):  
M. M. Sayeed ◽  
R. J. Adler ◽  
I. H. Chaudry ◽  
A. E. Baue
Keyword(s):  
Hemorrhagic Shock ◽  
Cell Volume ◽  
Volume Regulation ◽  
Cell Volume Regulation ◽  
Shed Blood ◽  
Average Value ◽  
Transmembrane Potentials ◽  
Relative Membrane Permeability

In this study we investigated in vivo changes in hepatic cellular electrolytes and resting transmembrane potentials (Em) during hemorrhagic shock. Hepatic Na-K transport and cell volume regulation were assessed in vitro. Rats were bled and the ensuing hypotension (40 mmHg) was maintained by returning 25-30% (intermediate-shock, IS) or 55-60% (late-shock, LS) of the shed blood. We resuscitated IS rats by reinfusion of all of the remaining shed blood and Ringer's lactate solution. Hepatic cellular Na and Cl increased and K decreased progressively with shock. Resuscitation of IS rats restored cell K and Cl but not Na to preshock levels. Em decreased from the control average value of -40 (mV) to -31 in IS and -19 in LS. Em was partially restored (-36 mV) after resuscitation. We evaluated changes in relative membrane permeability to Na and K (PNa/PK) with shock by assuming Em either to be a Na-K exchange diffusion potential or due to an unequally coupled movement of Na and K. These evaluations show a lack of effect of shock (IS, with or without resuscitation) on PNa/PK. Our observations are compatible with failure of an electrogenic Na pump in shock. This may be related to loss of hepatic cell volume regulation in shock.

Hemorrhagic shock impairs myocardial cell volume regulation and membrane integrity in dogs

1987 ◽  
Vol 252 (6) ◽  
pp. H1203-H1210
Author(s):  
J. W. Horton
Keyword(s):  
Hemorrhagic Shock ◽  
Cell Volume ◽  
Volume Regulation ◽  
Membrane Integrity ◽  
Cell Volume Regulation ◽  
Calcium Entry ◽  
Tissue Water ◽  
Total Tissue

An in vitro myocardial slice technique was used to quantitate alterations in cell volume regulation and membrane integrity after 2 h of hemorrhagic shock. After in vitro incubation in Krebs-Ringer-phosphate medium containing trace [14C]inulin, values (ml H2O/g dry wt) for control nonshocked myocardial slices were 4.03 +/- 0.11 (SE) for total water, 2.16 +/- 0.07 for inulin impermeable space, and 1.76 +/- 0.15 for inulin diffusible space. Shocked myocardial slices showed impaired response to cold incubation (0 degrees C, 60 min). After 2 h of in vivo shock, total tissue water, inulin diffusible space, and inulin impermeable space increased significantly (+19.2 +/- 2.4, +8.1 +/- 1.9, +34.4 +/- 6.1%, respectively) for subendocardium, whereas changes in subepicardium parameters were minimal. Shock-induced cellular swelling was accompanied by an increased total tissue sodium, but no change in tissue potassium. Calcium entry blockade in vivo (lidoflazine, 20 micrograms X kg-1 X min-1 during the last 60 min of shock) significantly reduced subendocardial total tissue water as compared with shock-untreated dogs. In addition, calcium entry blockade reduced shock-induced increases in inulin impermeable space and inulin diffusible space. In vitro myocardial slice studies confirm alterations in subendocardial membrane integrity after 2 h of in vivo hemorrhagic shock. Shock-induced abnormalities in myocardial cell volume regulation are reduced by calcium entry blockade in vivo.

Correlation between osmoregulation and cell volume regulation

1987 ◽  
Vol 252 (4) ◽  
pp. R768-R773
Author(s):  
M. A. Lang
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Osmotic Pressure ◽  
Cell Volume ◽  
Free Amino Acids ◽  
Volume Regulation ◽  
Free Amino ◽  
Cell Volume Regulation

The euryhaline crab, Callinectes sapidus, behaves both as an osmoregulator when equilibrated in salines in the range of 800 mosM and below and an osmoconformer when equilibrated in salines above 800 mosM. There exists a close correlation between osmoregulation seen in the whole animal in vivo and cell volume regulation studied in vitro. Hyperregulation of the hemolymph osmotic pressure and cell volume regulation both occurred in salines at approximately 800 mosM and below. During long-term equilibration of the crabs to a wide range of saline environments, the total concentration of hemolymph amino acids plus taurine remained below 3 mM. During the first 6 h after an acute osmotic stress to the whole animal, the hemolymph osmotic pressure and Na activity gradually decreased, whereas the free amino acids remained below 3 mM. As the hemolymph osmotic pressure decreased below approximately 850 mosM, the amino acid level began to increase to 17-25 mM. This change was primarily due to increases in glycine, proline, taurine, and alanine. The likely source of the increase in hemolymph free amino acids in vivo is the free amino acid loss from muscle cells observed during cell volume regulation in vitro.

Cell volume regulation in rabbit proximal straight tubule perfused in vitro

1987 ◽  
Vol 252 (5) ◽  
pp. F922-F932 ◽  
Author(s):  
K. L. Kirk ◽  
J. A. Schafer ◽  
D. R. DiBona
Keyword(s):  
Cell Volume ◽  
Volume Regulation ◽  
Time Course ◽  
Regulatory Volume Decrease ◽  
Cell Volume Regulation ◽  
Physiological Role ◽  
Cell Swelling ◽  
Computer Based

Volume regulation in the perfused proximal nephron of the rabbit was examined quantitatively with a computer-based method for estimating cell volume from differential interference-contrast microscopic images of isolated nephron segments. Following a hyperosmotic challenge (290-390 mosmol), the cells shrank as simple osmometers without a subsequent regulatory volume increase. Conversely, cell swelling induced by a hyposmotic challenge (290-190 mosmol) was completely reversed with a triphasic time course in which a rapid (less than 2 min) initial volume decline was followed by secondary swelling and shrinking phases. A similar regulatory volume decrease was observed following isosmotic cell swelling that was induced by exposure to 290 mosmol, urea-containing solutions. In addition, the cells partially reversed isosmotic swelling that was induced by the luminal replacement of a relatively impermeant cation (i.e., choline) with Na+ and a concomitant increase in luminal solute entry. Our results support two conclusions. First, there exist quantitative differences between the volume regulatory behaviors of perfused and nonperfused proximal tubules, the latter of which exhibit an incomplete and monotonic reversal of hyposmotic cell swelling (M. Dellasega and J. Grantham, Am. J. Physiol. 224: 1288-1294, 1973). Second, the primary physiological role of cell volume regulation in the proximal nephron may be to minimize isosmotic cell swelling associated with acute imbalances in the rates of cell solute entry and exit.

scholarly journals Regulation of liver cell volume and proteolysis by glucagon and insulin

1991 ◽  
Vol 278 (3) ◽  
pp. 771-777 ◽  
Author(s):  
S Vom Dahl ◽  
C Hallbrucker ◽  
F Lang ◽  
W Gerok ◽  
D Häussinger
Keyword(s):  
Cell Volume ◽  
Liver Cell ◽  
Intracellular Water ◽  
Cell Swelling ◽  
Isolated Perfused Rat Liver ◽  
Cell Shrinkage ◽  
Glucagon And Insulin ◽  
Opposing Effects ◽  
Water Space

The effects of insulin and glucagon on liver cell volume and proteolysis were studied in isolated perfused rat liver. The rate of proteolysis was assessed as [3H]leucine release from single-pass-perfused livers from rats which had been prelabelled in vivo by intraperitoneal injection of [3H]leucine. The intracellular water space was determined from the wash-out profiles of simultaneously added [3H]inulin and [14C]urea. In normo-osmotic (305 mosM) control perfusions the intracellular water space was 548 +/- 10 microliters/g wet mass (n = 44) and was increased by 16.5 +/- 2.6% (n = 6), i.e. by 85 +/- 14 microliters/g, after hypoosmotic exposure (225 mosM). Glucagon (0.1 microM) decreased the intracellular water space by 17 +/- 4% (n = 4), whereas insulin (35 nM) increased the intracellular water space by 9.3 +/- 1.4% (n = 15). Also, in isolated rat hepatocyte suspensions insulin (100 nM) caused cell swelling by 10.7 +/- 1.8% (n = 16), which was fully reversed by glucagon. In perfused liver, insulin-induced cell swelling was accompanied by a hepatic net K+ uptake (4.5 +/- 0.2 mumol/g) and an inhibition of proteolysis by 21 +/- 2% (n = 12); further addition of glucagon led to a net K+ release of 3.8 +/- 0.2 mumol/g (n = 7) and fully reversed the insulin effects on both cell volume and proteolysis. Similarly, insulin-induced cell swelling and inhibition of proteolysis were completely antagonized by hyperosmotic (385 mosM) cell shrinkage. Furthermore, cell swelling and inhibition of proteolysis after hypo-osmotic exposure or amino acid addition were reversed by glucagon-induced cell shrinkage. There was a close relationship between the extent of cell swelling and the inhibition of proteolysis, regardless of whether cell volume was modified by insulin, glucagon or aniso-osmotic exposure. The data show that glucagon and insulin are potent modulators of liver cell volume, at least in part by alterations of cellular K+ balance, and that their opposing effects on hepatic proteolysis can largely be explained by opposing effects on cell volume. It is hypothesized that hormone-induced alterations of cell volume may represent an important, not yet recognized, mechanism mediating hormonal effects on metabolism.

scholarly journals With-No-Lysine Kinase 3 (WNK3) stimulates glioma invasion by regulating cell volume

2011 ◽  
Vol 301 (5) ◽  
pp. C1150-C1160 ◽  
Author(s):  
Brian R. Haas ◽  
Vishnu A. Cuddapah ◽  
Stacey Watkins ◽  
Katie Jo Rohn ◽  
Tiffany E. Dy ◽  
...  
Keyword(s):  
Cell Volume ◽  
Cell Volume Regulation ◽  
Brain Parenchyma ◽  
Volume Changes ◽  
Glioma Invasion ◽  
Western Blots ◽  
Sodium Potassium ◽  
Complete Surgical Resection

Among the most prevalent and deadly primary brain tumors, high-grade gliomas evade complete surgical resection by diffuse invasion into surrounding brain parenchyma. Navigating through tight extracellular spaces requires invading glioma cells to alter their shape and volume. Cell volume changes are achieved through transmembrane transport of osmolytes along with obligated water. The sodium-potassium-chloride cotransporter isoform-1 (NKCC1) plays a pivotal role in this process, and previous work has demonstrated that NKCC1 inhibition compromises glioma invasion in vitro and in vivo by interfering with the required cell volume changes. In this study, we show that NKCC1 activity in gliomas requires the With-No-Lysine Kinase-3 (WNK3) kinase. Western blots of patient biopsies and patient-derived cell lines shows prominent expression of Ste-20-related, proline-alanine-rich kinase (SPAK), oxidative stress response kinase (OSR1), and WNK family members 1, 3, and 4. Of these, only WNK3 colocalized and coimmunoprecipitated with NKCC1 upon changes in cell volume. Stable knockdown of WNK3 using specific short hairpin RNA constructs completely abolished NKCC1 activity, as measured by the loss of bumetanide-sensitive cell volume regulation. Consequently, WNK3 knockdown cells showed a reduced ability to invade across Transwell barriers and lacked bumetanide-sensitive migration. This data indicates that WNK3 is an essential regulator of NKCC1 and that WNK3 activates NKCC1-mediated ion transport necessary for cell volume changes associated with cell invasion.

Hypotonic cell volume regulation in mouse medullary thick ascending limb: effects of ADH

1988 ◽  
Vol 255 (5) ◽  
pp. F962-F969 ◽  
Author(s):  
S. C. Hebert ◽  
A. Sun
Keyword(s):  
Cell Volume ◽  
Cell Volume Regulation ◽  
Cell Swelling ◽  
Thick Ascending Limb ◽  
Differential Interference Contrast Microscopy ◽  
Volume Regulatory Decrease ◽  
Medullary Thick Ascending Limb ◽  
Salt Absorption ◽  
Nephron Segment

Differential interference contrast microscopy was used in combination with standard electrophysiological techniques in the in vitro perfused mouse medullary thick ascending limb of Henle's loop (MAL) to evaluate the cell volume responses of this nephron segment during and following exposure to hypotonic media and to assess the role of antidiuretic hormone (ADH) and net salt absorption on the associated volume regulatory processes. Reductions in extracellular osmolality by 50 mosmol resulted in rapid increases in cell volume of approximately 20% with or without exposure to ADH. Cell volume recovery (volume-regulatory decrease, VRD) was much slower in the presence, than in the absence, of ADH. This hormone-mediated impairment of the VRD response could be overcome by the abolishment of net salt absorption with luminal 10(-4) M furosemide. An inverse linear relationship was observed between the rates of net salt absorption and VRD, indicating a finite ability of this nephron segment to enhance solute exit mechanisms whether induced by increases in transcellular traffic or by hypotonic cell swelling. Finally, returning to the isotonic media resulted in cell shrinkage under all conditions [+/- ADH and +(ADH and furosemide)] consistent with cell solute loss mediating VRD. However, recovery of cell volume back to the initial isotonic control value [post-VRD volume regulatory increase (VRI)] was only observed in ADH-treated tubules and was independent of net salt absorption. The post-VRD VRI response could be abolished by isohydric CO2-HCO3- removal or by addition of 10(-4) M amiloride to the peritubular medium. The latter results suggest that parallel Na+-H+ and Cl- -HCO3- exchangers located in basolateral membranes mediate the post-VRD VRI response.

scholarly journals Effects of hydration state on the synthesis and secretion of triacylglycerol by isolated rat hepatocytes. Implications for the actions of insulin and glucagon on hepatic secretion

1995 ◽  
Vol 312 (1) ◽  
pp. 57-62 ◽  
Author(s):  
V A Zammit
Keyword(s):  
Water Content ◽  
Cell Volume ◽  
Rat Hepatocytes ◽  
Cell Swelling ◽  
Cell Water ◽  
Cell Shrinkage ◽  
Isolated Rat Hepatocytes ◽  
Acute Changes ◽  
Isolated Rat

The effects of hepatocyte volume on the secretion of triacylglycerol were studied in order to test the suggestion that increases in the portal concentrations of osmolyte amino acids and metal ions during the prandial/early-absorptive phase may be involved in mediating the acute changes in glycerolipid metabolism observed in vivo [Zammit (1995) Biochem Soc. Trans. 23, 506-511]. Incubation of isolated rat hepatocytes with hypo-osmotic medium or in the presence of glutamine (in the presence or absence of leucine), conditions which gave an increase in cell water content of between 8 and 27%, resulted in a decrease in the rate of [14C]triacylglycerol (TAG) secretion when [14C]palmitate was used as substrate. The inhibition was proportional to the increase in cell water content. At low exogenous palmitate concentration (0.05 mM), the inhibition of [14C]TAG secretion was accompanied by a marked shift in the incorporation of label from TAG to phospholipid. In the presence of 0.5 mM palmitate this effect was attenuated, and in the presence of 1 mM palmitate it was abolished. Increased cell volume associated with incubation of hepatocytes with glutamine (in the presence or absence of leucine) also resulted in a decrease in the fraction of newly labelled TAG that was secreted into the medium. Decreased cell volume, achieved by incubation of hepatocytes with hyperosmotic medium (sufficient to decrease cell water content by approx. 9%) decreased overall [14C]TAG secretion, but did not affect the amount of label that was incorporated into phospholipid as a fraction of that incorporated into total glycerolipids. Cell shrinkage, however, diminished the fraction of newly labelled [14C]TAG that was secreted. When intracellular TAG was prelabelled with [3H]glycerol, it was found that cell shrinkage markedly inhibited (preformed) [3H]TAG secretion, whereas cell swelling did not affect this route of TAG secretion. The data are discussed in terms of the possible action of changes in cell hydration at the different loci at which hepatocyte TAG secretion is controlled, with reference to previous observations that both insulin and glucagon are able to inhibit TAG secretion in cultured rat hepatocytes and HepG2 cells.

scholarly journals Simulated diabetic ketoacidosis therapy in vitro elicits brain cell swelling via sodium-hydrogen exchange and anion transport

2015 ◽  
Vol 309 (4) ◽  
pp. E370-E379 ◽  
Author(s):  
Keeley L. Rose ◽  
Andrew J. Watson ◽  
Thomas A. Drysdale ◽  
Gediminas Cepinskas ◽  
Melissa Chan ◽  
...  
Keyword(s):  
Diabetic Ketoacidosis ◽  
Hydrogen Exchange ◽  
Brain Slices ◽  
Anion Transport ◽  
Brain Cell ◽  
Cell Swelling ◽  
Sodium Hydrogen ◽  
Disulphonic Acid

A common complication of type 1 diabetes mellitus is diabetic ketoacidosis (DKA), a state of severe insulin deficiency. A potentially harmful consequence of DKA therapy in children is cerebral edema (DKA-CE); however, the mechanisms of therapy-induced DKA-CE are unknown. Our aims were to identify the DKA treatment factors and membrane mechanisms that might contribute specifically to brain cell swelling. To this end, DKA was induced in juvenile mice with the administration of the pancreatic toxins streptozocin and alloxan. Brain slices were prepared and exposed to DKA-like conditions in vitro. Cell volume changes were imaged in response to simulated DKA therapy. Our experiments showed that cell swelling was elicited with isolated DKA treatment components, including alkalinization, insulin/alkalinization, and rapid reductions in osmolality. Methyl-isobutyl-amiloride, a nonselective inhibitor of sodium-hydrogen exchangers (NHEs), reduced cell swelling in brain slices elicited with simulated DKA therapy (in vitro) and decreased brain water content in juvenile DKA mice administered insulin and rehydration therapy (in vivo). Specific pharmacological inhibition of the NHE1 isoform with cariporide also inhibited cell swelling, but only in the presence of the anion transport (AT) inhibitor 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid. DKA did not alter brain NHE1 isoform expression, suggesting that the cell swelling attributed to the NHE1 was activity dependent. In conclusion, our data raise the possibility that brain cell swelling can be elicited by DKA treatment factors and that it is mediated by NHEs and/or coactivation of NHE1 and AT.

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