Membrane mechanisms in volume and pH regulation in vertebrate cells

Hoffmann, Else K.; Simonsen, Leif

doi:10.1152/physrev.1989.69.2.315

Cited by 874 publications

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The Involvement of Calcium Mobilization in the Calcium-Activated Potassium Currents Activated by Hyposmotic Swelling in Gastric Antral Circular Myocytes of the Guinea-Pig.

Piao

Liu²,

Lin³

et al. 2001

JJP

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The cells of vertebrates exposed to hyposmotic media, initially swell by osmotic water equilibration, but subsequently regulate their volume (regulatory volume decrease, RVD) by a loss of KCl and water (for review, see references [1][2][3]). The mechanisms of osmoregulatory K ϩ and Cl Ϫ efflux have not been completely understood. However, K ϩ and Cl Ϫ channels have been proposed to play an important role in RVD in various kinds of cells, such as those in frog urinary bladder [4], human lymphocytic cells [5], human epithelial cells [6], human platelets [7], and epithelial cells of frog skin [8].Both extracellular and intracellular [Ca 2ϩ ] are too low in animals to be useful as osmolytes. However, the Ca 2ϩ role during RVD has been recognized for many years. Many patch-clamp studies have found that the activation of volume-regulatory K ϩ channels is controlled by Ca 2ϩ (for review, see references [9,10]). Some experiments indicated that I K(Ca) was activated by an influx of Ca 2ϩ when the cell was superfused with hyposmotic solution [6,11,12]. Other experiments have shown that I K(Ca) is activated by an intracellular Ca 2ϩ signal that is released from intracellular calcium stores during RVD [13]. But the effect of hyposmotic swelling on I K(Ca) and the role of intracellular or extracellular Ca 2ϩ in gastric smooth muscle cells has not been investigated.In our previous study, we reported that the voltageoperated calcium current (I Ca ) was increased [14] and that the volume-sensitive chloride current (I Cl ) was activated by hyposmotic swelling [15] in gastric antral myocytes of the guinea-pig. In the present study, we Key words: gastric smooth muscle cell, Ca 2ϩ -activated K ϩ current, Ca 2ϩ -induced Ca 2ϩ release, swelling.Abstract: In our study of the effects of hyposmotic swelling on the Ca 2ϩ -activated potassium currents [I K(Ca) ] and its mechanism, we employed the whole-cell patch clamp technique using the gastric antral circular myocytes of the guinea-pig. Hyposmotic swelling efficiently increased I K(Ca) , and the extent of changes in I K(Ca) was sharply dependent on the osmolarity of the perfusion solutions. When the calcium-free solution (EGTA 10 M added in calcium-free solution) was superfused, I K(Ca) was not increased by the hyposmotic swelling. Gadolinium (Gd 3ϩ ) 100 nM, a blocker of the stretch-activated nonselective cation channel, blocked the activation of I K(Ca) induced by hyposmotic swelling, but nicardipine 5 M (the Ltype calcium channel blocker) did not. Heparin 3 mg/ml, a potent inhibitor of inositol triphosphate receptor (InsP 3 R), did not inhibit the response, and caffeine 1 mM (the agonist for calcium-induced calcium release [CICR]) imitated the effect of hyposmotic swelling. Ryanodine (15 M), markedly inhibited the effect. These results suggest that hyposmotic swelling activates I K(Ca) , and the activation is associated with CICR, which is triggered by extracellular calcium influx through the stretch-activated channel (SA channel).

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The Involvement of Calcium Mobilization in the Calcium-Activated Potassium Currents Activated by Hyposmotic Swelling in Gastric Antral Circular Myocytes of the Guinea-Pig.

Piao

Liu²,

Lin³

et al. 2001

JJP

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“…The EMP-induced increase in cell volume indicates a membrane leakage, also shown by a decreased t6Rb influx with a net flow of ions and water into the cell (Engstrom et al, 1990). This ion and water leakage may either be of non-specific nature or occur by different ion channels (Hoffman and Simonsen, 1989). Perifusion of the glioma cells with ion-channel blockers ouabain, bumetanide or furosemide concomitant with EMP appeared to block the increase in cell volume induced by EMP.…”

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confidence: 96%

“…This may be of particular importance since the blockers have been found to interfere also with the cytotoxic function of EMP during cell culture. Thus, it is possible that cell volume changes could serve as a rapid technique for predicting the cytotoxic activity of antineoplastic drugs.Keywords: cell volume; cytotoxicity; estramustine; microperifusion; potassium flux An intact cell volume is known to be of critical importance for the preservation of cell functions, including growth and proliferation (Hoffman and Simonsen, 1989). Extensive studies on cell volume regulation in the last few years indicate that a wide variety of cells share common regulatory capacities, although a pronounced diversity exists between different cell types in the nature of the ion transport systems involved.…”

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“…Extensive studies on cell volume regulation in the last few years indicate that a wide variety of cells share common regulatory capacities, although a pronounced diversity exists between different cell types in the nature of the ion transport systems involved. It is well known that transmembrane fluxes of cations are part of important cell functions, such as maintenance of the membrane potential regulation, intracellular pH (DeWeer, 1985), and volume regulation in anisotonic media (Hoffman and Simonsen, 1989). Predictive tumour sensitivity tests have received increasing attention, and several different predictive cellular and animal systems have been developed with varying degree of success (Chapman et al, 1989).…”

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“…Keywords: cell volume; cytotoxicity; estramustine; microperifusion; potassium flux An intact cell volume is known to be of critical importance for the preservation of cell functions, including growth and proliferation (Hoffman and Simonsen, 1989). Extensive studies on cell volume regulation in the last few years indicate that a wide variety of cells share common regulatory capacities, although a pronounced diversity exists between different cell types in the nature of the ion transport systems involved.…”

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Computerized detection of morphological changes to glioma cells during estramustine and ion-channel blocker perifusion

Behnam‐Motlagh

Jonsson²,

Engström³

et al. 1997

Br J Cancer

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Summary A perifusion technique for microscopy with computerized detection of early changes in cell morphology during continuous perifusion was used to show that the geometry of cultured glioma cells (MG-251) changes rapidly when they are exposed to estramustine phosphate (EMP). When the cells were exposed to 20 or 40 mg 1-' EMP, cell volume projected cell area (PCA) rapidly increased. When the Na+, K+-ATPase blocker ouabain (100 ,umol 1-') was added to the EMP (40 mg 1-') perifusion, the acute EMP response was eradicated. When the PCA curve for ouabain alone was subtracted from the curve of combined ouabain and EMP perifusion, the resulting curve showed that ouabain completely blocked the EMP-induced increase in PCA. When the Na+, K+, Cl-co-transport inhibitors bumetanide (10 lmol 1-'), or furosemide (100 ,umol 1-'), were added to EMP (40 mg 1-'), the acute increase in PCA seen for EMP alone was also completely blocked. This study shows that inhibitors of ion transmembrane transport can modify EMP-induced cell volume increases. This may be of particular importance since the blockers have been found to interfere also with the cytotoxic function of EMP during cell culture. Thus, it is possible that cell volume changes could serve as a rapid technique for predicting the cytotoxic activity of antineoplastic drugs.Keywords: cell volume; cytotoxicity; estramustine; microperifusion; potassium flux An intact cell volume is known to be of critical importance for the preservation of cell functions, including growth and proliferation (Hoffman and Simonsen, 1989). Extensive studies on cell volume regulation in the last few years indicate that a wide variety of cells share common regulatory capacities, although a pronounced diversity exists between different cell types in the nature of the ion transport systems involved. It is well known that transmembrane fluxes of cations are part of important cell functions, such as maintenance of the membrane potential regulation, intracellular pH (DeWeer, 1985), and volume regulation in anisotonic media (Hoffman and Simonsen, 1989). Predictive tumour sensitivity tests have received increasing attention, and several different predictive cellular and animal systems have been developed with varying degree of success (Chapman et al, 1989). There is, thus, still a strong need for more effective predictive tests of drug sensitivity in clinical oncology.Estramustine phosphate (EMP), a cytotoxic nor-nitrogen mustard derivative of oestradiol 1 7p-phosphate, is generally accepted in the treatment of advanced prostatic carcinoma (Madajewics et al, 1980), and recently it has been shown to exert considerable cytotoxic effects on several glioma cell lines von Schoultz et al, 1990). In the present study, we have investigated the effect of bumetanide and furosemide, inhibitors of Na+, K+, Cl-co-transport, and ouabain, an inhibitor of Na+, K+-ATPase, on the cytotoxic effect of EMP. This was done by means of a new microscopic technique that provides the ability to follow early alterations in cell size an...

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Cell size distribution as a parameter for the predetermination of exponential growth during repeated batch cultivation of CHO cells

Seewöster

Lehmann

1997

Biotechnol. Bioeng.

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The routine measurement of the cell size distribution of a Chinese hamster ovary (CHO) cell population during a repeated batch process enables the predetermination of exponential growth even 24 h before the population enters the log phase, due to a short but significantly increased cell size during the lag phase. A prolongation of the stationary phase causes to progressive limitation in asparagine, serine, and ethanolamine. Such extended limitation influences the duration of the following lag phase and obviously induces a synchronization of the cell population that can be monitored easily by a fast cell size analyzing technique. © 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 793–797, 1997.

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Membrane mechanisms in volume and pH regulation in vertebrate cells

Cited by 874 publications

References 0 publications

The Involvement of Calcium Mobilization in the Calcium-Activated Potassium Currents Activated by Hyposmotic Swelling in Gastric Antral Circular Myocytes of the Guinea-Pig.

The Involvement of Calcium Mobilization in the Calcium-Activated Potassium Currents Activated by Hyposmotic Swelling in Gastric Antral Circular Myocytes of the Guinea-Pig.

Computerized detection of morphological changes to glioma cells during estramustine and ion-channel blocker perifusion

Cell size distribution as a parameter for the predetermination of exponential growth during repeated batch cultivation of CHO cells

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