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

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 grad...

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Main Authors: Yizeng Li, Xiaohan Zhou, Sean X. Sun
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-06-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2021.683686/full
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author Yizeng Li
Xiaohan Zhou
Sean X. Sun
Sean X. Sun
Sean X. Sun
author_facet Yizeng Li
Xiaohan Zhou
Sean X. Sun
Sean X. Sun
Sean X. Sun
author_sort Yizeng Li
collection DOAJ
description 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.
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spelling doaj.art-437820fdc33c434bb21bcdfd0f7a205e2022-12-21T21:24:38ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-06-01910.3389/fcell.2021.683686683686Hydrogen, Bicarbonate, and Their Associated Exchangers in Cell Volume RegulationYizeng Li0Xiaohan Zhou1Sean X. Sun2Sean X. Sun3Sean X. Sun4Department of Mechanical Engineering, Kennesaw State University, Marietta, GA, United StatesDepartment of Physics, University of Toronto, Toronto, ON, CanadaDepartment of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, United StatesInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, United StatesCenter for Cell Dynamics, Johns Hopkins School of Medicine, Baltimore, MD, United StatesCells 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.683686/fullcell volume regulationpHhydrogenbicarbonatesodium-hydrogen exchangerchloride-bicarbonate exchanger
spellingShingle Yizeng Li
Xiaohan Zhou
Sean X. Sun
Sean X. Sun
Sean X. Sun
Hydrogen, Bicarbonate, and Their Associated Exchangers in Cell Volume Regulation
Frontiers in Cell and Developmental Biology
cell volume regulation
pH
hydrogen
bicarbonate
sodium-hydrogen exchanger
chloride-bicarbonate exchanger
title Hydrogen, Bicarbonate, and Their Associated Exchangers in Cell Volume Regulation
title_full Hydrogen, Bicarbonate, and Their Associated Exchangers in Cell Volume Regulation
title_fullStr Hydrogen, Bicarbonate, and Their Associated Exchangers in Cell Volume Regulation
title_full_unstemmed Hydrogen, Bicarbonate, and Their Associated Exchangers in Cell Volume Regulation
title_short Hydrogen, Bicarbonate, and Their Associated Exchangers in Cell Volume Regulation
title_sort hydrogen bicarbonate and their associated exchangers in cell volume regulation
topic cell volume regulation
pH
hydrogen
bicarbonate
sodium-hydrogen exchanger
chloride-bicarbonate exchanger
url https://www.frontiersin.org/articles/10.3389/fcell.2021.683686/full
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AT seanxsun hydrogenbicarbonateandtheirassociatedexchangersincellvolumeregulation
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