Contribution of Na+-K+-Cl−cotransporter to high-[K+]o- induced swelling and EAA release in astrocytes

2002 ◽  
Vol 282 (5) ◽  
pp. C1136-C1146 ◽  
Author(s):  
Gui Su ◽  
Douglas B. Kintner ◽  
Dandan Sun
Keyword(s):  
Cell Volume ◽  
Recovery Rate ◽  
Glutamate Release ◽  
Volume Changes ◽  
Control Value ◽  
Astrocyte Swelling ◽  
High K ◽  
Stimulation Of

We hypothesized that high extracellular K+ concentration ([K+]o)-mediated stimulation of Na+-K+-Cl− cotransporter isoform 1 (NKCC1) may result in a net gain of K+ and Cl−and thus lead to high-[K+]o-induced swelling and glutamate release. In the current study, relative cell volume changes were determined in astrocytes. Under 75 mM [K+]o, astrocytes swelled by 20.2 ± 4.9%. This high-[K+]o-mediated swelling was abolished by the NKCC1 inhibitor bumetanide (10 μM, 1.0 ± 3.1%; P < 0.05). Intracellular36Cl− accumulation was increased from a control value of 0.39 ± 0.06 to 0.68 ± 0.05 μmol/mg protein in response to 75 mM [K+]o. This increase was significantly reduced by bumetanide ( P < 0.05). Basal intracellular Na+ concentration ([Na+]i) was reduced from 19.1 ± 0.8 to 16.8 ± 1.9 mM by bumetanide ( P < 0.05). [Na+]i decreased to 8.4 ± 1.0 mM under 75 mM [K+]o and was further reduced to 5.2 ± 1.7 mM by bumetanide. In addition, the recovery rate of [Na+]i on return to 5.8 mM [K+]o was decreased by 40% in the presence of bumetanide ( P < 0.05). Bumetanide inhibited high-[K+]o-induced 14C-labeledd-aspartate release by ∼50% ( P < 0.05). These results suggest that NKCC1 contributes to high-[K+]o-induced astrocyte swelling and glutamate release.

Astrocytes from Na+-K+-Cl−cotransporter-null mice exhibit absence of swelling and decrease in EAA release

2002 ◽  
Vol 282 (5) ◽  
pp. C1147-C1160 ◽  
Author(s):  
Gui Su ◽  
Douglas B. Kintner ◽  
Michael Flagella ◽  
Gary E. Shull ◽  
Dandan Sun
Keyword(s):  
Cell Volume ◽  
Glutamate Release ◽  
Volume Increase ◽  
Regulatory Volume Increase ◽  
A Value ◽  
Cortical Astrocytes ◽  
High K ◽  
Stimulation Of

We reported previously that inhibition of Na+-K+-Cl− cotransporter isoform 1 (NKCC1) by bumetanide abolishes high extracellular K+concentration ([K+]o)-induced swelling and intracellular Cl− accumulation in rat cortical astrocytes. In this report, we extended our study by using cortical astrocytes from NKCC1-deficient (NKCC1−/−) mice. NKCC1 protein and activity were absent in NKCC1−/− astrocytes. [K+]o of 75 mM increased NKCC1 activity approximately fourfold in NKCC1+/+ cells ( P< 0.05) but had no effect in NKCC1−/− astrocytes. Intracellular Cl− was increased by 70% in NKCC1+/+ astrocytes under 75 mM [K+]o ( P < 0.05) but remained unchanged in NKCC1−/− astrocytes. Baseline intracellular Na+ concentration ([Na+]i) in NKCC1+/+ astrocytes was 19.0 ± 0.5 mM, compared with 16.9 ± 0.3 mM [Na+]i in NKCC1−/− astrocytes ( P < 0.05). Relative cell volume of NKCC1+/+ astrocytes increased by 13 ± 2% in 75 mM [K+]o, compared with a value of 1.0 ± 0.5% in NKCC1−/− astrocytes ( P < 0.05). Regulatory volume increase after hypertonic shrinkage was completely impaired in NKCC1−/− astrocytes. High-[K+]o-induced 14C-labeledd-aspartate release was reduced by ∼30% in NKCC1−/− astrocytes. Our study suggests that stimulation of NKCC1 is required for high-[K+]o-induced swelling, which contributes to glutamate release from astrocytes under high [K+]o.

scholarly journals Effects of estradiol on ischemic factor-induced astrocyte swelling and AQP4 protein abundance

2011 ◽  
Vol 301 (1) ◽  
pp. C204-C212 ◽  
Author(s):  
Jennifer M. Rutkowsky ◽  
Breanna K. Wallace ◽  
Phyllis M. Wise ◽  
Martha E. O'Donnell
Keyword(s):  
Ischemic Stroke ◽  
Cell Volume ◽  
Cerebral Edema ◽  
Glucose Deprivation ◽  
Aquaporin 4 ◽  
Oxygen Glucose Deprivation ◽  
Protein Abundance ◽  
Astrocyte Swelling ◽  
Aqp4 Protein ◽  
Stimulation Of

In the early hours of ischemic stroke, cerebral edema forms as Na, Cl, and water are secreted across the blood-brain barrier (BBB) and astrocytes swell. We have shown previously that ischemic factors, including hypoxia, aglycemia, and arginine vasopressin (AVP), stimulate BBB Na-K-Cl cotransporter (NKCC) and Na/H exchanger (NHE) activities and that inhibiting NKCC and/or NHE by intravenous bumetanide and/or HOE-642 reduces edema and infarct in a rat model of ischemic stroke. Estradiol also reduces edema and infarct in this model and abolishes ischemic factor stimulation of BBB NKCC and NHE. There is evidence that NKCC and NHE also participate in ischemia-induced swelling of astrocytes. However, little is known about estradiol effects on astrocyte cell volume. In this study, we evaluated the effects of AVP (100 nM), hypoxia (7.5% O2), aglycemia, hypoxia (2%)/aglycemia [oxygen glucose deprivation (OGD)], and estradiol (1–100 nM) on astrocyte cell volume using 3- O-methyl-d-[3H]glucose equilibration methods. We found that AVP, hypoxia, aglycemia, and OGD (30 min to 5 h) each significantly increased astrocyte cell volume, and that estradiol (30–180 min) abolished swelling induced by AVP or hypoxia, but not by aglycemia or OGD. Bumetanide and/or HOE-642 also abolished swelling induced by AVP but not aglycemia. Abundance of aquaporin-4, known to participate in ischemia-induced astrocyte swelling, was significantly reduced following 7-day but not 2- or 3-h estradiol exposures. Our findings suggest that hypoxia, aglycemia, and AVP each contribute to ischemia-induced astrocyte swelling, and that the edema-attenuating effects of estradiol include reduction of hypoxia- and AVP-induced astrocyte swelling and also reduction of aquaporin-4 abundance.

scholarly journals Cell volume and bile acid excretion

1992 ◽  
Vol 288 (2) ◽  
pp. 681-689 ◽  
Author(s):  
D Häussinger ◽  
C Hallbrucker ◽  
N Saha ◽  
F Lang ◽  
W Gerok
Keyword(s):  
Amino Acids ◽  
Cell Volume ◽  
Liver Cell ◽  
Bile Flow ◽  
Cell Swelling ◽  
Isolated Perfused Rat Liver ◽  
Cell Shrinkage ◽  
Volume Changes ◽  
Close Relationship ◽  
Stimulation Of

The interaction between cell volume and taurocholate excretion into bile was studied in isolated perfused rat liver. Cell swelling due to hypo-osmotic exposure, addition of amino acids or insulin stimulated taurocholate excretion into bile and bile flow, whereas hyperosmotic cell shrinkage inhibited these. These effects were explained by changes in Vmax of taurocholate excretion into bile: Vmax. increased from about 300 to 700 nmol/min per g after cell swelling by 12-15% caused by either hypo-osmotic exposure or addition of amino acids under normo-osmotic conditions. Steady-state taurocholate excretion into bile was not affected when the influent K+ concentration was increased from 6 to 46 mM or decreased to 1 mM with iso-osmoticity being maintained by corresponding changes in the influent Na+ concentration. Replacement of 40 mM-NaCl by 80 mM-sucrose decreased taurocholate excretion into bile by about 70%; subsequent hypo-osmotic exposure by omission of sucrose increased taurocholate excretion to 160%. Only minor, statistically insignificant, effects of aniso-osmotic cell volume changes on the appearance of bolus-injected horseradish peroxidase in bile were observed. Taurocholate (400 microM) exhibited a cholestatic effect during hyperosmotic cell shrinkage, but not during hypo-osmotic cell swelling. Both taurocholate and tauroursodeoxycholate increased liver cell volume. Tauroursodeoxycholate stimulated taurocholate (100 microM) excretion into bile. This stimulatory effect was strongly dependent on the extent of tauroursodeoxycholate-induced cell swelling. During continuous infusion of taurocholate (100 microM) further addition of tauroursodeoxycholate at concentrations of 20, 50 and 100 microM increased cell volume by 10, 8 and 2% respectively, in parallel with a stimulation of taurocholate excretion into bile by 29, 27 and 9% respectively. There was a close relationship between the extent of cell volume changes and taurocholate excretion into bile, regardless of whether cell volume was modified by tauroursodeoxycholate, amino acids or aniso-osmotic exposure. The data suggest that: (i) liver cell volume is one important factor determining bile flow and biliary taurocholate excretion; (ii) swelling-induced stimulation of taurocholate excretion into bile is probably not explained by alterations of the membrane potential; (iii) bile acids modulate liver cell volume; (iv) taurocholate-induced cholestasis may depend on cell volume; (v) stimulation of taurocholate excretion into bile by tauroursodeoxycholate can largely be explained by tauroursodeoxycholate-induced cell swelling.

Effects of apical membrane Cl(-)-formate exchange on cell volume in rabbit proximal tubule

1990 ◽  
Vol 258 (3) ◽  
pp. F530-F536 ◽  
Author(s):  
L. Schild ◽  
P. S. Aronson ◽  
G. Giebisch
Keyword(s):  
Proximal Tubule ◽  
Cell Volume ◽  
Apical Membrane ◽  
Cell Swelling ◽  
Volume Changes ◽  
Proximal Tubule Cells ◽  
Volume Increase ◽  
Tubule Lumen ◽  
Stimulation Of

We used real-time recordings of cell volume changes to test for the role of the Cl(-)-formate exchanger in mediating NaCl entry across the apical membrane of rabbit proximal tubule cells. In the absence of extracellular Cl-, 0.5 and 5 mM formate in the tubule lumen induced an increase in cell volume of 1 and 9%, respectively. Formate-induced cell swelling was reduced by alkalinizing the tubule lumen or by addition of luminal amiloride (2 mM), indicating that the increase in cell volume results from the intracellular accumulation of Na-formate via nonionic diffusion of formic acid in parallel with Na(+)-H+ exchange. The cell volume increase induced by 0.5 mM formate was potentiated (from 1 to 4%) by Cl-, as expected for a formate-mediated stimulation of NaCl uptake via parallel Cl(-)-formate exchange and Na(+)-H+ exchange across the apical membrane. By contrast, the cell volume increase induced by 5 mM formate was attenuated (from 9 to 4%) by Cl-. The attenuating effect of Cl- on formate-induced cell swelling required the operation of the apical membrane Cl(-)-formate exchanger. The effect of 1:1 Cl(-)-formate exchange to attenuate formate-induced cell swelling can be explained if the cell possesses a volume-activated anion exit pathway, most likely at the basolateral cell membrane, that is capable of mediating the efflux of Cl- but not formate from the cell.

Stimulation of Intestinal Na+/H+ Exchange by Cell Volume Changes during Fasting and Refeeding in Rats

1995 ◽  
Vol 209 (4) ◽  
pp. 354-359 ◽  
Author(s):  
J.-J. Hajjar ◽  
W. Aziz ◽  
T. F. P. Molski ◽  
R. I. Sha'afi
Keyword(s):  
Cell Volume ◽  
Volume Changes ◽  
Fasting And Refeeding ◽  
Stimulation Of

Liver cell hydration and integrin signaling

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Michele Bonus ◽  
Dieter Häussinger ◽  
Holger Gohlke
Keyword(s):  
Cell Volume ◽  
Liver Cell ◽  
Cell Function ◽  
The Other ◽  
Signaling Cascades ◽  
Integrin Signaling ◽  
Volume Changes ◽  
The One ◽  
And Oxidative Stress

Abstract Liver cell hydration (cell volume) is dynamic and can change within minutes under the influence of hormones, nutrients, and oxidative stress. Such volume changes were identified as a novel and important modulator of cell function. It provides an early example for the interaction between a physical parameter (cell volume) on the one hand and metabolism, transport, and gene expression on the other. Such events involve mechanotransduction (osmosensing) which triggers signaling cascades towards liver function (osmosignaling). This article reviews our own work on this topic with emphasis on the role of β1 integrins as (osmo-)mechanosensors in the liver, but also on their role in bile acid signaling.

Effects of pyruvate on the energetics of rat ventricles stunned by ischemia–reperfusion

2014 ◽  
Vol 92 (5) ◽  
pp. 386-398 ◽  
Author(s):  
Patricia Bonazzola ◽  
María Inés Ragone ◽  
Alicia E. Consolini
Keyword(s):  
Confocal Microscopy ◽  
Heat Release ◽  
Dynamic Balance ◽  
Ischemia Reperfusion ◽  
Rat Hearts ◽  
High K ◽  
Energetic State ◽  
Contractile Recovery ◽  
Stimulation Of

Pyruvate (Pyr) was proposed as an additive to cold high-K+–low-Ca2+ cardioplegia (CPG) to protect the heart during surgery. We explored whether Pyr and CPG would work synergistically to protect rat hearts from stunning during ischemia–reperfusion (I/R). We measured the heat release and contractility of perfused ventricles during I/R, and the cytosolic and mitochondrial [Ca2+] in cardiomyocytes by confocal microscopy. We found that under cold-CPG (30 °C), 10 mmol·L−1 Pyr reduced the post-ischemic contractile recovery (PICR) as well as muscle economy, when added either before ischemia or during I/R, which was reversed by blockade of UCam. In noncardioplegic hearts, Pyr was cardioprotective when it was present during I/R, more so at 37 °C than at 30 °C, with improved economy. In cardiomyocytes, the addition of Pyr to CPG slightly increased the mitochondrial [Ca2+] but decreased cytosolic [Ca2+]. The results suggest that Pyr only protects hearts from stunning when present before ischemia and during reperfusion, and that it dampens the cardioprotective properties of CPG. The mechanisms underlying such different behavior depend on the dynamic balance between Pyr stimulation of the energetic state and mitochondrial Ca2+ uptake. Our results support the use of Pyr in stunned hearts, but not in cold high-K+ cardioplegia.

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