scholarly journals Hydrogen, Bicarbonate, and Their Associated Exchangers in Cell Volume Regulation

Author(s):  
Yizeng Li ◽  
Xiaohan Zhou ◽  
Sean X. Sun

Cells lacking a stiff cell wall, e.g., mammalian cells, must actively regulate their volume to maintain proper cell function. On the time scale that protein production is negligible, water flow in and out of the cell determines the cell volume variation. Water flux follows hydraulic and osmotic gradients; the latter is generated by various ion channels, transporters, and pumps in the cell membrane. Compared to the widely studied roles of sodium, potassium, and chloride in cell volume regulation, the effects of proton and bicarbonate are less understood. In this work, we use mathematical models to analyze how proton and bicarbonate, combined with sodium, potassium, chloride, and buffer species, regulate cell volume upon inhibition of ion channels, transporters, and pumps. The model includes several common, widely expressed ion transporters and focuses on obtaining generic outcomes. Results show that the intracellular osmolarity remains almost constant before and after cell volume change. The steady-state cell volume does not depend on water permeability. In addition, to ensure the stability of cell volume and ion concentrations, cells need to develop redundant mechanisms to maintain homeostasis, i.e., multiple ion channels or transporters are involved in the flux of the same ion species. These results provide insights for molecular mechanisms of cell volume regulation with additional implications for water-driven cell migration.

Physiology ◽  
1990 ◽  
Vol 5 (3) ◽  
pp. 112-119 ◽  
Author(s):  
SA Lewis ◽  
P Donaldson

Exposure of many vertebrate cells to solutions more dilute or concentrated than the physiological "norm" results in an initial increase or decrease in cell volume followed by a recovery of volume toward a normal value. Although the basic strategy for volume regulation is the same for cell types studied, the mechanism by which the cell regulates ion channels appears to be tissue dependent.


1977 ◽  
Vol 232 (1) ◽  
pp. F42-F49 ◽  
Author(s):  
J. J. Grantham ◽  
C. M. Lowe ◽  
M. Dellasega ◽  
B. R. Cole

The intracellular content of K and Na was measured in isolated nonperfused proximal straight renal tubules (PST) in order to determine the mode of cell volume regulation in hypotonic bathing media. Immersion in hypotonic medium caused PST to lose K and Na (with anions) in a magnitude sufficient to account for the regulation of cell volume. Hypothermia (10 degrees C) blocked cell volume regulation in hypotonic medium by promoting net accumulation of Na, although K loss was equivalent to that observed at 37 degrees C. Ouabain (10(-5) M) caused rapid loss of cell K and gain of Na in an isotonic bath, but the glycoside did not inhibit the subsequent adjustment of cell volume in hypotonic medium. In hypotonic medium ouabain-treated tubules lost Na, but not K, to account for hypotonic volume adjustment of PST in ouabain. We conclude that proximal straight tubules extrude electrolytes (K, Na, and anions) in the adjustment of cell volume in hypotonic media; in normal tubules K and Na are lost whereas Na moves primarily in ouabain-treated tubules. The adjustment of size through the extrusion of intracellular solutes in dilutional states appears to be a general property of mammalian cells.


2011 ◽  
Vol 116 (4) ◽  
pp. 343-349 ◽  
Author(s):  
Shintaro Yamamoto ◽  
Satomi Kita ◽  
Takuya Iyoda ◽  
Toshiki Yamada ◽  
Takahiro Iwamoto

2021 ◽  
Vol 55 (S1) ◽  
pp. 71-88

The regulation of cell volume is an essential cellular process in nearly every living organism. The importance of volume regulation in immune cells cannot be understated, as it ensures proper cellular function and effective immune response. These cells utilize ion channels and transporters to maintain volume homeostasis through rapid ion transport across the cell membrane. Immune cells express mechanisms controlling regulatory volume decrease (RVD), regulatory volume increase (RVI), proliferative RVD, and apoptotic volume decrease (AVD). In this review, we summarize recent studies examining the importance of several ion channels, particularly potassium and chloride channels in regulating ion transport during osmotic stress, and in immune cell function, activation, proliferation, and death. We also review the key mechanisms functioning in immune cell proliferation and apoptosis. They serve a crucial role in maintaining adequate ionic concentrations, mediating immune cell activation, and generating proliferative pathways. These regulatory mechanisms play key roles in the function and survival of immune cells, as impaired volume regulation contributes to the pathophysiology of various disorders. A complete understanding of immune cell volume regulatory mechanisms may be a starting point for the development of therapeutic agents targeting these ion channels to treat inflammatory diseases.


2019 ◽  
Author(s):  
Nicolas A. Perez-Gonzalez ◽  
Nash D. Rochman ◽  
Kai Yao ◽  
Jiaxiang Tao ◽  
Minh-Tam Tran Le ◽  
...  

AbstractHow mammalian cells regulate their physical size is currently poorly understood, in part due to the difficulty of accurately quantifying cell volume in a high throughput manner. Here, using the fluorescence exclusion method, we demonstrate that the mechanosensitive transcriptional regulators YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are novel regulators of single cell volume. We report that the role of YAP/TAZ in cell volume regulation must go beyond its influence on total cell cycle duration or the cell shape to explain the observed changes in volume. Moreover, for our experimental conditions, volume regulation by YAP/TAZ is independent of mTOR. Instead, we find YAP/TAZ directly impacts the cell division volume. Based on the idea that YAP/TAZ is a mechanosensor, we find that inhibiting the assembly of myosin and cell tension slows cell cycle progression from G1 to S. These results suggest that YAP/TAZ and the Hippo pathway may be modulating cell volume in combination with cytoskeletal tension during cell cycle progression.


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