Extracellular Acid-Base Balance and Ion Transport Between Body Fluid Compartments

Seifter, Julian L.; Chang, Hou‐Tai

doi:10.1152/physiol.00007.2017

Cited by 48 publications

(45 citation statements)

References 78 publications

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“…Cells keep their acid-base regulation by using many metabolic enzymes, transporters and pH sensors. Their activities produce several acid-base equivalent species, including proton (H + ), lactate and carbon dioxide (CO 2 ) (Sanhueza et al, 2016), which are transported through plasma membrane (Seifter and Chang, 2017). The most important transporters that mediate pH homeostasis are ( Fig.…”

Section: Channels and Transporters Involved In Regulation Of Extracelmentioning

confidence: 99%

Extracellular pH and lung infections in cystic fibrosis

Massip-Copiz

Santa‐Coloma

2018

European Journal of Cell Biology

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Cystic fibrosis (CF) is an autosomal recessive disease caused by CFTR mutations. It is characterized by high NaCl concentration in sweat and the production of a thick and sticky mucus, occluding secretory ducts, intestine and airways, accompanied by chronic inflammation and infections of the lungs. This causes a progressive and lethal decline in lung function. Therefore, finding the mechanisms driving the high susceptibility to lung infections has been a key issue. For decades the prevalent hypothesis was that a reduced airway surface liquid (ASL) volume and composition, and the consequent increased mucus concentration (dehydration), create an environment favoring infections. However, a few years ago, in a pig model of CF, the Na/K concentrations and the ASL volume were found intact. Immediately a different hypothesis arose, postulating a reduced ASL pH as the cause for the increased susceptibility to infections, due to a diminished bicarbonate secretion through CFTR. Noteworthy, a recent report found normal ASL pH values in CF children and in cultured primary airway cells, challenging the ASL pH hypothesis. On the other hand, recent evidences revitalized the hypothesis of a reduced ASL secretion. Thus, the role of the ASL pH in the CF is still a controversial matter. In this review we discuss the basis that sustain the role of CFTR in modulating the extracellular pH, and the recent results sustaining the different points of view. Finding the mechanisms of CFTR signaling that determine the susceptibility to infections is crucial to understand the pathophysiology of CF and related lung diseases.

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Section: Channels and Transporters Involved In Regulation Of Extracelmentioning

confidence: 99%

Extracellular pH and lung infections in cystic fibrosis

Massip-Copiz

Santa‐Coloma

2018

European Journal of Cell Biology

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“…Figure 2 B shows the possible causes of the lowering of ASL pH depending on endogenous or exogenous acidity. Extracellular and ASL acidification may be caused in four different ways: H + derived from the physiological process of restoring prestimulus conditions, carried out by all cells through the expulsion of excess protons, generated by acidifying enzymes, to return to the steady state; cells can use acid extruders as exchangers and channels to transfer H + externally; the Na + -H + exchanger (NHE) in some cells is the major acid-extruder, also the Cystic fibrosis transmembrane conductance regulator (CFTR) plays an important role in the acidification of the ASL [ 117 ]; in addition, the excess protons in the cytosol may exit the cell via voltage-gated proton channels (Hv1), TRP channels, plasma membrane vacuolar V-type H + -ATPase [ 126 , 132 , 133 , 134 , 135 , 136 ], and diffusion [ 125 ]; The degranulation of phagocytes, such as macrophages and granulocyte neutrophils and eosinophils [ 69 , 135 , 137 , 138 ], produced as a defensive inflammatory action [ 24 , 126 ] in response to the stimulus. This acidifying action may be significant and long lasting, and is therefore the basis for chronic disease; The degranulation of mast cells and basophils, caused by the stimulus, the basis of the acute allergic response [ 77 , 78 , 80 , 84 , 138 ], as described above in Figure 1 .…”

Section: Resultsmentioning

confidence: 99%

Environmental and Endogenous Acids Can Trigger Allergic-Type Airway Reactions

Molinari¹,

Molinari²,

Nervo

2020

IJERPH

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Inflammatory allergic and nonallergic respiratory disorders are spreading worldwide and often coexist. The root cause is not clear. This review demonstrates that, from a biochemical point of view, it is ascribable to protons (H+) released into cells by exogenous and endogenous acids. The hypothesis of acids as the common cause stems from two considerations: (a) it has long been known that exogenous acids present in air pollutants can induce the irritation of epithelial surfaces, particularly the airways, inflammation, and bronchospasm; (b) according to recent articles, endogenous acids, generated in cells by phospholipases, play a key role in the biochemical mechanisms of initiation and progression of allergic-type reactions. Therefore, the intracellular acidification and consequent Ca2+ increase, induced by protons generated by either acid pollutants or endogenous phospholipases, may constitute the basic mechanism of the multimorbidity of these disorders, and environmental acidity may contribute to their spread.

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“…Ion-free diets, regardless of sugar type and concentration, rescued the edema. This suggests that CG4928 knockdown flies can handle endogenous ion levels, indicating that there are other biochemical pathways that have the capability to use, store, and handle the faulty potassium fluxes ( Seifter and Chang, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

CG4928 Is Vital for Renal Function in Fruit Flies and Membrane Potential in Cells: A First In-Depth Characterization of the Putative Solute Carrier UNC93A

Ceder

Aggarwal

Hosseini

et al. 2020

Front. Cell Dev. Biol.

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The number of transporter proteins that are not fully characterized is immense. Here, we used Drosophila melanogaster and human cell lines to perform a first in-depth characterization of CG4928, an ortholog to the human UNC93A, of which little is known. Solute carriers regulate and maintain biochemical pathways important for the body, and malfunctioning transport is associated with multiple diseases. Based on phylogenetic analysis, CG4928 is closely related to human UNC93A and has a secondary and a tertiary protein structure and folding similar to major facilitator superfamily transporters. Ubiquitous knockdown of CG4928 causes flies to have a reduced secretion rate from the Malpighian tubules; altering potassium content in the body and in the Malpighian tubules, homologous to the renal system; and results in the development of edema. The edema could be rescued by using amiloride, a common diuretic, and by maintaining the flies on ion-free diets. CG4928-overexpressing cells did not facilitate the transport of sugars and amino acids; however, proximity ligation assay revealed that CG4928 co-localized with TASK 1 channels. Overexpression of CG4928 resulted in induced apoptosis and cytotoxicity, which could be restored when cells were kept in high-sodium media. Furthermore, the basal membrane potential was observed to be disrupted. Taken together, the results indicate that CG4928 is of importance for generating the cellular membrane potential by an unknown manner. However, we speculate that it most likely acts as a regulator or transporter of potassium flows over the membrane.

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Extracellular Acid-Base Balance and Ion Transport Between Body Fluid Compartments

Cited by 48 publications

References 78 publications

Extracellular pH and lung infections in cystic fibrosis

Extracellular pH and lung infections in cystic fibrosis

Environmental and Endogenous Acids Can Trigger Allergic-Type Airway Reactions

CG4928 Is Vital for Renal Function in Fruit Flies and Membrane Potential in Cells: A First In-Depth Characterization of the Putative Solute Carrier UNC93A

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