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Else K Hoffmann - One of the best experts on this subject based on the ideXlab platform.
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ion channels involved in Cell Volume Regulation effects on migration proliferation and programmed Cell death in non adherent eat Cells and adherent ela Cells
Cellular Physiology and Biochemistry, 2011Co-Authors: Else K HoffmannAbstract:This mini review outlines studies of Cell Volume Regulation in two closely related mammalian Cell lines: nonadherent Ehrlich ascites tumour Cells (EATC) and adherent Ehrlich Lettre ascites (ELA) Cells. Focus is on the regulatory Volume decrease (RVD) that occurs after Cell swelling, the Volume regulatory ion channels involved, and the mechanisms (Cellular signalling pathways) that regulate these channels. Finally, I shall also briefly review current investigations in these two Cell lines that focuses on how changes in Cell Volume can regulate Cell functions such as Cell migration, proliferation, and programmed Cell death.
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physiology of Cell Volume Regulation in vertebrates
Physical Review, 2009Co-Authors: Else K Hoffmann, Ian Henry Lambert, Stine F PedersenAbstract:The ability to control Cell Volume is pivotal for Cell function. Cell Volume perturbation elicits a wide array of signaling events, leading to protective (e.g., cytoskeletal rearrangement) and adap...
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Cell Volume Regulation physiology and pathophysiology
Acta Physiologica, 2008Co-Authors: Ian Henry Lambert, Else K Hoffmann, Stine F PedersenAbstract:Cell Volume perturbation initiates a wide array of intraCellular signalling cascades, leading to protective and adaptive events and, in most cases, activation of Volume-regulatory osmolyte transport, water loss, and hence restoration of Cell Volume and Cellular function. Cell Volume is challenged not only under physiological conditions, e.g. following accumulation of nutrients, during epithelial absorption/secretion processes, following hormonal/autocrine stimulation, and during induction of apoptosis, but also under pathophysiological conditions, e.g. hypoxia, ischaemia and hyponatremia/hypernatremia. On the other hand, it has recently become clear that an increase or reduction in Cell Volume can also serve as a specific signal in the Regulation of physiological processes such as transepithelial transport, Cell migration, proliferation and death. Although the mechanisms by which Cell Volume perturbations are sensed are still far from clear, significant progress has been made with respect to the nature of the sensors, transducers and effectors that convert a change in Cell Volume into a physiological response. In the present review, we summarize recent major developments in the field, and emphasize the relationship between Cell Volume Regulation and organism physiology/pathophysiology.
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sensors and signal transduction pathways in vertebrate Cell Volume Regulation
Contributions To Nephrology, 2006Co-Authors: Else K Hoffmann, Stine F PedersenAbstract:The ability to control Cell Volume is fundamental for proper Cell function. This review highlights recent advances in the understanding of the complex sequences of events by which acute Cell Volume perturbation alters the activity of osmolyte transport proteins in Cells from vertebrate organisms. After Cell swelling, the main effectors in the process of regulatory Volume decrease are swelling-activated K(+) and Cl(-) channels, a taurine efflux pathway, and KCl cotransport. After Cell shrinkage, the main effectors in the process of regulatory Volume increase are Na(+)/H(+) exchange, Na(+), K(+), 2Cl(-) cotransport, and in some Cells, shrinkageactivated Na(+) channels. All of these proteins are regulated in a unique manner by Cell Volume perturbations. The molecular identity of most, although not all, of these transport pathways is now known. Among other important advances, this has lead to the identification of transporter binding partners such as protein kinases and phosphatases, cytoskeletal elements and lipids. Considerable progress has also been made recently in understanding the upstream elements in Volume sensing and Volume-sensitive signal transduction, and salient features of these systems will be discussed. In contrast to the simple pathway of osmosensing in yeast, Cells from vertebrate organisms appear to exhibit multiple Volume sensing systems, the specific mechanism(s) activated being Cell type- and stimulus-dependent. Candidate sensors include integrins and growth factor receptors, while other early events include Regulation of Rho family GTP binding proteins, Ste20-related protein kinases, and phospholipases, as well as cytoskeletal reorganization, Transient Receptor Potential channel-mediated Ca(2+) influx, and generation of reactive oxygen species.
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swelling activated ion channels functional Regulation in Cell swelling proliferation and apoptosis
Acta Physiologica, 2006Co-Authors: A Stutzin, Else K HoffmannAbstract:Cell Volume Regulation is one of the most fundamental homeostatic mechanisms and essential for normal Cellular function. At the same time, however, many physiological mechanisms are associated with regulatory changes in Cell size meaning that the set point for Cell Volume Regulation is under physiological control. Thus, Cell Volume is under a tight and dynamic control and abnormal Cell Volume Regulation will ultimately lead to severe Cellular dysfunction, including alterations in Cell proliferation and Cell death. This review describes the different swelling-activated ion channels that participate as key players in the maintenance of normal steady-state Cell Volume, with particular emphasis on the intraCellular signalling pathways responsible for their Regulation during hypotonic stress, Cell proliferation and apoptosis.
Gregory J Wilson - One of the best experts on this subject based on the ideXlab platform.
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enhanced Cell Volume Regulation a key mechanism in local and remote ischemic preconditioning
American Journal of Physiology-cell Physiology, 2014Co-Authors: Roberto J Diaz, Peter H Backx, Kordan Harvey, Taneya Hossain, Alina Hinek, Azadeh Boloorchi, Gregory J WilsonAbstract:We have previously shown that ischemic preconditioning (IPC) protection against necrosis in whole hearts and in both fresh and cultured cardiomyocytes, as well as the improved regulatory Volume dec...
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enhanced Cell Volume Regulation in cyclosporin a cardioprotection
Cardiovascular Research, 2013Co-Authors: Roberto J Diaz, Kelly Fernandes, Yuliya Lytvyn, Krista M Hawrylyshyn, Kordan Harvey, Taneya Hossain, Alina Hinek, Gregory J WilsonAbstract:Aims Cyclosporin A (CsA), has been shown to protect against ischaemia/reperfusion injury presumably by its inhibition of mitochondrial permeability transition pore opening through cyclophilin D inhibition. We examine if CsA cardioprotection involves a Cell Volume regulatory mechanism. Methods and Results To address this issue, cultured rabbit cardiomyocytes were subjected to the following protocols: i) Cardiomyocytes were treated with 200 nM CsA either given for 10 min followed by 10 min of washout prior to 30-min hypo-osmotic stress (200mOsm) or administered throughout 75-min simulated ischaemia/60-min simulated reperfusion. Cell necrosis and Cell swelling were determined by trypan blue staining and Cell Volume measurements, respectively. ii) SPQ(6-methoxy-N-(3-sulfopropyl)quinolinium) dye loaded cardiomyocytes were treated with 200 nM CsA for 10 min followed by 10 min washout and intraCellular Cl- concentration measured (Cl- efflux). iii) 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimi-dazolylcarbocyanine iodide(JC-1) loaded cardiomyocytes were treated with 200 nM CsA to inhibit mitochondrial membrane potential (ΔΨm) dissipation (an index of mitochondria permeability transition pore opening) by either valinomycin (2 µM) or ischemia/reperfusion injury. Cl- channels were blocked by indanyloxyacetic acid 94 (IAA-94, 50 µM). CsA not only significantly (P<0.001) reduced the % of dead Cells following simulated ischaemia/reperfusion but it also triggered an efflux of Cl- hence enhancing cardiomyocyte Cell Volume regulatory response. CsA protection against Cell necrosis and its effect on Cl- transport/Volume Regulation were all blocked by IAA-94. IAA-94 had no effect on ΔΨm. Conclusion These data indicate that CsA protects against Cell necrosis at least in part by enhancing cardiomyocyte Volume Regulation, and not simply by inhibiting MPTP opening. (word count is 247)
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enhanced Cell Volume Regulation a key protective mechanism of ischemic preconditioning in rabbit ventricular myocytes
Journal of Molecular and Cellular Cardiology, 2003Co-Authors: Roberto J Diaz, Charles E. Ganote, Stephen C Armstrong, Michelle Batthish, Peter H Backx, Gregory J WilsonAbstract:Accumulation of osmotically active metabolites, which create an osmotic gradient estimated at ~60 mOsM, and Cell swelling are prominent features of ischemic myocardial Cell death. This study tests the hypothesis that reduction of ischemic swelling by enhanced Cell Volume Regulation is a key mechanism in the delay of ischemic myocardial Cell death by ischemic preconditioning (IPC). Experimental protocols address whether: (i) IPC triggers a Cell Volume Regulation mechanism that reduces cardiomyocyte swelling during subsequent index ischemia; (ii) this reduction in ischemic Cell swelling is sufficient in magnitude to account for the IPC protection; (iii) the molecular mechanism that mediates IPC also mediates Cell Volume Regulation. Two experimental models with rabbit ventricular myocytes were studied: freshly isolated pelleted myocytes and 48-h cultured myocytes. Myocytes were preconditioned either by distinct short simulated ischemia (SI)/simulated reperfusion protocols (IPC), or by subjecting myocytes to a pharmacological preconditioning (PPC) protocol (1 microM calyculin A, or 1 microM N(6)-2-(4-aminophenyl)ethyladenosine (APNEA), prior to subjecting them to either different durations of long SI or 30 min hypo-osmotic stress. Cell death (percent blue square myocytes) was monitored by trypan blue staining. Cell swelling was determined by either the bromododecane Cell flotation assay (qualitative) or video/confocal microscopy (quantitative). Simulated ischemia induced myocyte swelling in both the models. In pelleted myocytes, IPC or PPC with either calyculin A or APNEA produced a marked reduction of ischemic Cell swelling as determined by the Cell floatation assay. In cultured myocytes, IPC substantially reduced ischemic Cell swelling (P < 0.001). This IPC effect on ischemic Cell swelling was related to an IPC and PPC (with APNEA) mediated triggering of Cell Volume regulatory decrease (RVD). IPC and APNEA also significantly (P < 0.001) reduced hypo-osmotic Cell swelling. This IPC and APNEA effect was blocked by either adenosine receptor, PKC or Cl(-) channel inhibition. The osmolar equivalent for IPC protection approximated 50-60 mOsM, an osmotic gradient similar to the estimated ischemic osmotic load for preconditioned and non-preconditioned myocytes. The results suggest that Cell Volume Regulation is a key mechanism that accounts for most of the IPC protection in cardiomyocytes.
Philippe Poujeol - One of the best experts on this subject based on the ideXlab platform.
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Role of TASK2 potassium channels regarding Volume Regulation in primary cultures of mouse proximal tubules.
Journal of General Physiology, 2003Co-Authors: Herve Barriere, Radia Belfodil, Isabelle Rubera, Michel Tauc, Florian Lesage, Chantal Poujeol, Nicolas Guy, Jacques Barhanin, Philippe PoujeolAbstract: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 beta-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 microM 293B, but blocked by 500 microM quinidine and 10 microM 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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role of task2 potassium channels regarding Volume Regulation in primary cultures of mouse proximal tubules
The Journal of General Physiology, 2003Co-Authors: Herve Barriere, Radia Belfodil, Isabelle Rubera, Michel Tauc, Florian Lesage, Chantal Poujeol, Nicolas Guy, Jacques Barhanin, Philippe PoujeolAbstract: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.
Alessandro Sardini - One of the best experts on this subject based on the ideXlab platform.
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Cell Volume Regulation and swelling-activated chloride channels
Biochimica et Biophysica Acta, 2003Co-Authors: Alessandro Sardini, Joanna Amey, Karsten Henrich Weylandt, Miguel A. Valverde, Muriel Nobles, Christopher F. HigginsAbstract:Abstract Maintenance of a constant Volume is essential for normal Cell function. Following Cell swelling, as a consequence of reduction of extraCellular osmolarity or increase of intraCellular content of osmolytes, animal Cells are able to restore their original Volume by activation of potassium and chloride conductances. The loss of these ions, followed passively by water, is responsible for the homeostatic response called regulatory Volume decrease (RVD). Activation of a chloride conductance upon Cell swelling is a key step in RVD. Several proteins have been proposed as candidates for this chloride conductance. The status of the field is reviewed, with particular emphasis on ClC-3, a member of the ClC family which has been recently proposed as the chloride channel involved in Cell Volume Regulation.
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human clc 3 is not the swelling activated chloride channel involved in Cell Volume Regulation
Journal of Biological Chemistry, 2001Co-Authors: Karsten Henrich Weylandt, Joanna Amey, Miguel A. Valverde, Christopher F. Higgins, Muriel Nobles, Selina Raguz, Mario Diaz, Candida Nastrucci, Alessandro SardiniAbstract:Abstract Volume Regulation is essential for normal Cell function. A key component of the Cells' response to Volume changes is the activation of a channel, which elicits characteristic chloride currents (ICl, Swell). The molecular identity of this channel has been controversial. Most recently, ClC-3, a protein highly homologous to the ClC-4 and ClC-5 channel proteins, has been proposed as being responsible for ICl, Swell (1). Subsequently, however, other reports have suggested that ClC-3 may generate chloride currents with characteristics clearly distinct from ICl, Swell. Significantly different tissue distributions for ClC-3 have also been reported, and it has been suggested that two isoforms of ClC-3 may be expressed with differing functions. In this study we generated a series of Cell lines expressing variants of ClC-3 to rigorously address the question of whether or not ClC-3 is responsible for ICl, Swell. The data demonstrate that ClC-3 is not responsible for ICl, Swell and has no role in regulatory Volume decrease, furthermore, ClC-3 is not activated by intraCellular calcium and fails to elicit chloride currents under any conditions tested. Expression of ClC-3 was shown to be relatively tissue-specific, with high levels in the central nervous system and kidney, and in contrast to previous reports, is essentially absent from heart. This distribution is also inconsistent with the previous proposed role in Cell Volume Regulation.
Roberto J Diaz - One of the best experts on this subject based on the ideXlab platform.
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enhanced Cell Volume Regulation a key mechanism in local and remote ischemic preconditioning
American Journal of Physiology-cell Physiology, 2014Co-Authors: Roberto J Diaz, Peter H Backx, Kordan Harvey, Taneya Hossain, Alina Hinek, Azadeh Boloorchi, Gregory J WilsonAbstract:We have previously shown that ischemic preconditioning (IPC) protection against necrosis in whole hearts and in both fresh and cultured cardiomyocytes, as well as the improved regulatory Volume dec...
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enhanced Cell Volume Regulation in cyclosporin a cardioprotection
Cardiovascular Research, 2013Co-Authors: Roberto J Diaz, Kelly Fernandes, Yuliya Lytvyn, Krista M Hawrylyshyn, Kordan Harvey, Taneya Hossain, Alina Hinek, Gregory J WilsonAbstract:Aims Cyclosporin A (CsA), has been shown to protect against ischaemia/reperfusion injury presumably by its inhibition of mitochondrial permeability transition pore opening through cyclophilin D inhibition. We examine if CsA cardioprotection involves a Cell Volume regulatory mechanism. Methods and Results To address this issue, cultured rabbit cardiomyocytes were subjected to the following protocols: i) Cardiomyocytes were treated with 200 nM CsA either given for 10 min followed by 10 min of washout prior to 30-min hypo-osmotic stress (200mOsm) or administered throughout 75-min simulated ischaemia/60-min simulated reperfusion. Cell necrosis and Cell swelling were determined by trypan blue staining and Cell Volume measurements, respectively. ii) SPQ(6-methoxy-N-(3-sulfopropyl)quinolinium) dye loaded cardiomyocytes were treated with 200 nM CsA for 10 min followed by 10 min washout and intraCellular Cl- concentration measured (Cl- efflux). iii) 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimi-dazolylcarbocyanine iodide(JC-1) loaded cardiomyocytes were treated with 200 nM CsA to inhibit mitochondrial membrane potential (ΔΨm) dissipation (an index of mitochondria permeability transition pore opening) by either valinomycin (2 µM) or ischemia/reperfusion injury. Cl- channels were blocked by indanyloxyacetic acid 94 (IAA-94, 50 µM). CsA not only significantly (P<0.001) reduced the % of dead Cells following simulated ischaemia/reperfusion but it also triggered an efflux of Cl- hence enhancing cardiomyocyte Cell Volume regulatory response. CsA protection against Cell necrosis and its effect on Cl- transport/Volume Regulation were all blocked by IAA-94. IAA-94 had no effect on ΔΨm. Conclusion These data indicate that CsA protects against Cell necrosis at least in part by enhancing cardiomyocyte Volume Regulation, and not simply by inhibiting MPTP opening. (word count is 247)
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enhanced Cell Volume Regulation a key protective mechanism of ischemic preconditioning in rabbit ventricular myocytes
Journal of Molecular and Cellular Cardiology, 2003Co-Authors: Roberto J Diaz, Charles E. Ganote, Stephen C Armstrong, Michelle Batthish, Peter H Backx, Gregory J WilsonAbstract:Accumulation of osmotically active metabolites, which create an osmotic gradient estimated at ~60 mOsM, and Cell swelling are prominent features of ischemic myocardial Cell death. This study tests the hypothesis that reduction of ischemic swelling by enhanced Cell Volume Regulation is a key mechanism in the delay of ischemic myocardial Cell death by ischemic preconditioning (IPC). Experimental protocols address whether: (i) IPC triggers a Cell Volume Regulation mechanism that reduces cardiomyocyte swelling during subsequent index ischemia; (ii) this reduction in ischemic Cell swelling is sufficient in magnitude to account for the IPC protection; (iii) the molecular mechanism that mediates IPC also mediates Cell Volume Regulation. Two experimental models with rabbit ventricular myocytes were studied: freshly isolated pelleted myocytes and 48-h cultured myocytes. Myocytes were preconditioned either by distinct short simulated ischemia (SI)/simulated reperfusion protocols (IPC), or by subjecting myocytes to a pharmacological preconditioning (PPC) protocol (1 microM calyculin A, or 1 microM N(6)-2-(4-aminophenyl)ethyladenosine (APNEA), prior to subjecting them to either different durations of long SI or 30 min hypo-osmotic stress. Cell death (percent blue square myocytes) was monitored by trypan blue staining. Cell swelling was determined by either the bromododecane Cell flotation assay (qualitative) or video/confocal microscopy (quantitative). Simulated ischemia induced myocyte swelling in both the models. In pelleted myocytes, IPC or PPC with either calyculin A or APNEA produced a marked reduction of ischemic Cell swelling as determined by the Cell floatation assay. In cultured myocytes, IPC substantially reduced ischemic Cell swelling (P < 0.001). This IPC effect on ischemic Cell swelling was related to an IPC and PPC (with APNEA) mediated triggering of Cell Volume regulatory decrease (RVD). IPC and APNEA also significantly (P < 0.001) reduced hypo-osmotic Cell swelling. This IPC and APNEA effect was blocked by either adenosine receptor, PKC or Cl(-) channel inhibition. The osmolar equivalent for IPC protection approximated 50-60 mOsM, an osmotic gradient similar to the estimated ischemic osmotic load for preconditioned and non-preconditioned myocytes. The results suggest that Cell Volume Regulation is a key mechanism that accounts for most of the IPC protection in cardiomyocytes.