scholarly journals Evolution of our understanding of cell volume regulation by the pump-leak mechanism

2019 ◽  
Vol 151 (4) ◽  
pp. 407-416 ◽  
Author(s):  
Alan R. Kay ◽  
Mordecai P. Blaustein
Keyword(s):  
Cell Volume ◽  
Sodium Pump ◽  
Fundamental Problem ◽  
Cell Volume Regulation ◽  
Osmotic Gradient ◽  
Animal Cells ◽  
Pivotal Study ◽  
History Of ◽  
Mechanistic Basis ◽  
Intracellular Ions

All animal cells are surrounded by a flexible plasma membrane that is permeable to water and to small ions. Cells thus face a fundamental problem: the considerable tension that their membranes would experience if the osmotic influx of water, driven by the presence of impermeant intracellular ions, was left unopposed. The pivotal study that described the cell’s remedy for this impending osmotic catastrophe—the “pump-leak mechanism” (PLM)—was published in the Journal of General Physiology by Tosteson and Hoffman in 1960. Their work revealed how the sodium pump stabilizes cell volume by eliminating the osmotic gradient. Here we describe the mechanistic basis of the PLM, trace the history of its discovery, and place it into the context of our current understanding.

scholarly journals Cell Death Induction and Protection by Activation of Ubiquitously Expressed Anion/Cation Channels. Part 2: Functional and Molecular Properties of ASOR/PAC Channels and Their Roles in Cell Volume Dysregulation and Acidotoxic Cell Death

2021 ◽  
Vol 9 ◽  
Author(s):  
Yasunobu Okada ◽  
Kaori Sato-Numata ◽  
Ravshan Z. Sabirov ◽  
Tomohiro Numata
Keyword(s):  
Cell Death ◽  
Cell Volume ◽  
Apoptotic Cell ◽  
Cell Volume Regulation ◽  
Anion Channel ◽  
Cell Swelling ◽  
Dimensional Structure ◽  
Cation Channels ◽  
Anion Channels ◽  
Animal Cells

For survival and functions of animal cells, cell volume regulation (CVR) is essential. Major hallmarks of necrotic and apoptotic cell death are persistent cell swelling and shrinkage, and thus they are termed the necrotic volume increase (NVI) and the apoptotic volume decrease (AVD), respectively. A number of ubiquitously expressed anion and cation channels play essential roles not only in CVR but also in cell death induction. This series of review articles address the question how cell death is induced or protected with using ubiquitously expressed ion channels such as swelling-activated anion channels, acid-activated anion channels, and several types of TRP cation channels including TRPM2 and TRPM7. In the Part 1, we described the roles of swelling-activated VSOR/VRAC anion channels. Here, the Part 2 focuses on the roles of the acid-sensitive outwardly rectifying (ASOR) anion channel, also called the proton-activated chloride (PAC) anion channel, which is activated by extracellular protons in a manner sharply dependent on ambient temperature. First, we summarize phenotypical properties, the molecular identity, and the three-dimensional structure of ASOR/PAC. Second, we highlight the unique roles of ASOR/PAC in CVR dysfunction and in the induction of or protection from acidotoxic cell death under acidosis and ischemic conditions.

scholarly journals Ouabain-Induced Cytoplasmic Vesicles and Their Role in Cell Volume Maintenance

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
M. A. Russo ◽  
E. Morgante ◽  
A. Russo ◽  
G. D. van Rossum ◽  
M. Tafani
Keyword(s):  
Cell Volume ◽  
Cell Volume Regulation ◽  
Extracellular Fluid ◽  
Bile Canaliculus ◽  
Volume Control ◽  
Osmotic Gradient ◽  
Water Composition ◽  
Mammalian Tissues ◽  
Metabolic Conditions ◽  
Cell Volume Control

Cellular swelling is controlled by an active mechanism of cell volume regulation driven by a Na+/K+-dependent ATPase and by aquaporins which translocate water along the osmotic gradient. Na+/K+-pump may be blocked by ouabain, a digitalic derivative, by inhibition of ATP, or by drastic ion alterations of extracellular fluid. However, it has been observed that some tissues are still able to control their volume despite the presence of ouabain, suggesting the existence of other mechanisms of cell volume control. In 1977, by correlating electron microscopy observation with ion and water composition of liver slices incubated in different metabolic conditions in the presence or absence of ouabain, we observed that hepatocytes were able to control their volume extruding water and recovering ion composition in the presence of ouabain. In particular, hepatocytes were able to sequester ions and water in intracellular vesicles and then secrete them at the bile canaliculus pole. We named this “vesicular mechanism of cell volume control.” Afterward, this mechanism has been confirmed by us and other laboratories in several mammalian tissues. This review summarizes evidences regarding this mechanism, problems that are still pending, and questions that need to be answered. Finally, we shortly review the importance of cell volume control in some human pathological conditions.

Effect of collagenase and ouabain on renal cell volume in hypotonic media

1980 ◽  
Vol 238 (6) ◽  
pp. F491-F498 ◽  
Author(s):  
M. A. Linshaw ◽  
J. J. Grantham
Keyword(s):  
Hydrostatic Pressure ◽  
Cell Volume ◽  
Volume Regulation ◽  
Sodium Pump ◽  
Cell Volume Regulation ◽  
Apparent Volume ◽  
Normal Operation ◽  
Renal Tubules ◽  
Straight Tubules ◽  
Do So

Proximal straight tubules (S2 segments) swell rapidly in hypotonic media, but within a few minutes their volume returns toward control levels due to extrusion of K, Na, Cl, and water from the cytoplasm. In the present studies we determined the extent to which hydrostatic pressure (derived from the elastic tubule basement membrane (TBM) as the tubule enlarged in hypotonic medium) contributed to the regulation of cell volume. Removal of the TBM by collagenase had no effect on cell volume regulation in otherwise normal tubules. By contrast, tubules treated with ouabain, though they appeared to regulate their volumes in hypotonic media, were unable to do so in the presence of glycoside if the TBM had been removed with collagenase. This latter result is interpreted to show that hydrostatic pressure generated by extension of the TBM can cause “apparent” volume regulation when the sodium pump is blocked by ouabain. We conclude that normal proximal renal tubules regulate cell volume in hypotonic solutions by mechanisms that are dependent on the normal operation of the classical sodium pump.

Microfluidic Cell Volume Biosensor for High Throughput Drug Screening

2004 ◽  
Vol 845 ◽  
Author(s):  
Daniel A. Ateya ◽  
Frederick Sachs ◽  
Susan Z. Hua
Keyword(s):  
Cell Volume ◽  
Volume Change ◽  
Cell Volume Regulation ◽  
High Sensitivity ◽  
Rapid Screening ◽  
Osmotic Gradient ◽  
Physiological Processes ◽  
High Throughput Drug Screening ◽  
Microfluidic Chamber ◽  
Pharmaceutical Agents

ABSTRACTThe maintenance of cell volume is critical to health. Cell volume change reflects many biological and physiological processes. We have developed a lab-chip to measure cell volume change in real-time with high sensitivity and resolution, and applicable to both adherent and suspended cell populations. The volume change was detected by measuring the impedance of extra-cellular solution within a microfluidic chamber containing the cells. Using microfabrication to make precise chamber dimensions, volume change can be detected in response to an osmotic gradient <1mOsm. The sensor provides rapid screening of pharmaceutical agents affecting cell volume. We have screened for peptides that affect cell volume regulation and found one in spider venom that inhibits at ∼100pM.

An Introduction to Nonlinear Chemical Dynamics

1998 ◽  
Author(s):  
Irving R. Epstein ◽  
John A. Pojman
Keyword(s):  
Flow Reactor ◽  
Chemical Dynamics ◽  
Design Data ◽  
Chemical Oscillators ◽  
Starting Point ◽  
Hands On ◽  
Undergraduate Laboratory ◽  
History Of ◽  
Mechanistic Basis ◽  
Nonlinear Chemical Dynamics

Just a few decades ago, chemical oscillations were thought to be exotic reactions of only theoretical interest. Now known to govern an array of physical and biological processes, including the regulation of the heart, these oscillations are being studied by a diverse group across the sciences. This book is the first introduction to nonlinear chemical dynamics written specifically for chemists. It covers oscillating reactions, chaos, and chemical pattern formation, and includes numerous practical suggestions on reactor design, data analysis, and computer simulations. Assuming only an undergraduate knowledge of chemistry, the book is an ideal starting point for research in the field. The book begins with a brief history of nonlinear chemical dynamics and a review of the basic mathematics and chemistry. The authors then provide an extensive overview of nonlinear dynamics, starting with the flow reactor and moving on to a detailed discussion of chemical oscillators. Throughout the authors emphasize the chemical mechanistic basis for self-organization. The overview is followed by a series of chapters on more advanced topics, including complex oscillations, biological systems, polymers, interactions between fields and waves, and Turing patterns. Underscoring the hands-on nature of the material, the book concludes with a series of classroom-tested demonstrations and experiments appropriate for an undergraduate laboratory.

Mechanisms responsible for cell volume regulation during hyperkalemic cardioplegic arrest

2000 ◽  
Vol 70 (2) ◽  
pp. 633-638
Author(s):  
Xiwu Sun ◽  
Christopher T Ducko ◽  
Eric M Hoenicke ◽  
Karen Reigle ◽  
Ralph J Damiano
Keyword(s):  
Cell Volume ◽  
Volume Regulation ◽  
Cell Volume Regulation ◽  
Cardioplegic Arrest
Sign in / Sign up

Export Citation Format

Share Document