Intracellular pH transients estimated from a physical-chemical model of the cellular acid-base control system. Possible effect of the intra-cellular pH on some parameters of contraction and electrical activation of cardiac cells

1976 ◽  
Vol 84 (4) ◽  
pp. 891-892
Author(s):  
A. de Hemptinne ◽  
R. Marrannes
Keyword(s):  
Control System ◽  
Intracellular Ph ◽  
Cardiac Cells ◽  
Electrical Activation ◽  
Chemical Model ◽  
Acid Base ◽  
Physical Chemical

Role of bicarbonate in the regulation of intracellular pH in the mammalian ventricular myocyte

2002 ◽  
Vol 80 (5) ◽  
pp. 579-596 ◽  
Author(s):  
Richard D Vaughan-Jones ◽  
Kenneth W Spitzer
Keyword(s):  
Intracellular Ph ◽  
Cardiac Contractility ◽  
Physiological Role ◽  
Cardiac Cells ◽  
Whole Body ◽  
Bicarbonate Transport ◽  
Acid Base ◽  
Bicarbonate Transporter ◽  
Coupling Protein

Bicarbonate is important for pHi control in cardiac cells. It is a major part of the intracellular buffer apparatus, it is a substrate for sarcolemmal acid-equivalent transporters that regulate intracellular pH, and it contributes to the pHo sensitivity of steady-state pHi, a phenomenon that may form part of a whole-body response to acid/base disturbances. Both bicarbonate and H+/OH– transporters participate in the sarcolemmal regulation of pHi, namely Na+–HCO3– cotransport (NBC), Cl––HCO3– exchange (i.e., anion exchange, AE), Na+–H+ exchange (NHE), and Cl––OH– exchange (CHE). These transporters are coupled functionally through changes of pHi, while pHi is linked to [Ca2+]i through secondary changes in [Na+]i mediated by NBC and NHE. Via such coupling, decreases of pHo and pHi can ultimately lead to an elevation of [Ca2+]i, thereby influencing cardiac contractility and electrical rhythm. Bicarbonate is also an essential component of an intracellular carbonic buffer shuttle that diffusively couples cytoplasmic pH to the sarcolemma and minimises the formation of intracellular pH microdomains. The importance of bicarbonate is closely linked to the activity of the enzyme carbonic anhydrase (CA). Without CA activity, intracellular bicarbonate-dependent buffering, membrane bicarbonate transport, and the carbonic shuttle are severely compromised. There is a functional partnership between CA and HCO3– transport. Based on our observations on intracellular acid mobility, we propose that one physiological role for CA is to act as a pH-coupling protein, linking bulk pH to the allosteric H+ control sites on sarcolemmal acid/base transporters.Key words: bicarbonate transporter, pHi, heart, ventricular.

Effect of systemic acid-base disorders on ileal intracellular pH and ion transport

1986 ◽  
Vol 250 (5) ◽  
pp. G588-G593 ◽  
Author(s):  
J. D. Wagner ◽  
P. Kurtin ◽  
A. N. Charney
Keyword(s):  
Intracellular Ph ◽  
Respiratory Acidosis ◽  
Strong Correlations ◽  
Sprague Dawley ◽  
Acid Base ◽  
Ileal Mucosa ◽  
Arterial Pco2 ◽  
Co2 Partial Pressure ◽  
Arterial Ph ◽  
Acute Metabolic Acidosis

We previously reported that changes in ileal net Na absorption correlated with arterial pH, changes in net HCO3 secretion correlated with the plasma HCO3 concentration, and changes in net Cl absorption correlated with arterial CO2 partial pressure (PCO2) during the systemic acid-base disorders. To determine whether changes in intracellular pH (pHi) and HCO3 concentration [( HCO3]i) mediated these effects, we measured pHi and calculated [HCO3]i in the distal ileal mucosa of anesthetized, mechanically ventilated Sprague-Dawley rats using 5,5-[14C]dimethyloxazolidine-2,4,-dione and [3H]inulin. Rats were studied during normocapnia, acute respiratory acidosis, and alkalosis, and uncompensated and pH-compensated acute metabolic acidosis and alkalosis. When animals in all groups were considered, mucosal pHi was not altered, but there were strong correlations between mucosal [HCO3]i and both arterial PCO2 (r = 0.97) and [HCO3] (r = 0.61). When we considered the rates of ileal electrolyte transport that characterized these acid-base disorders [A. N. Charney and L.P. Haskell, Am. J. Physiol. 245 (Gastrointest. Liver Physiol. 8): G230-G235, 1983], we found strong correlations between mucosal [HCO3]i and both net Cl absorption (r = 0.88) and net HCO3 secretion (r = 0.82). These findings suggest that the systemic acid-base disorders do not affect ileal mucosal pHi but do alter mucosal [HCO3]i as a consequence of altered arterial PCO2 and [HCO3]. The effects of these disorders on ileal net Cl absorption and HCO3 secretion may be mediated by changes in [HCO3]i. Arterial pH does not appear to alter ileal Na absorption through changes in the mucosal acid-base milieu.

scholarly journals The Boron & De Weer Model of Intracellular pH Regulation

2020 ◽  
Author(s):  
Rossana Occhipinti ◽  
Soroush Safaei ◽  
Peter J. Hunter ◽  
Walter F. Boron
Keyword(s):  
Cell Membrane ◽  
Intracellular Ph ◽  
Ph Regulation ◽  
Quantitative Model ◽  
Historical Background ◽  
Acid Base ◽  
Experimental Conditions ◽  
Subsequent Work ◽  
Energy Dependent ◽  
Parameter Values

The classic Boron & De Weer (1976) paper provided the first evidence of active regulation of pH} in cells by an energy-dependent acid-base transporter. These authors also developed a quantitative model --- comprising passive fluxes of acid-base equivalents across the cell membrane, intracellular reactions, and an active transport mechanism in the cell membrane (modelled as a proton pump) --- to help interpret their measurements of intracellular pH under perturbations of both extracellular CO2/HCO3- and extracellular NH3/NH4+. This Physiome paper seeks to make that model, and the experimental conditions under which it was developed, available in a reproducible and well-documented form, along with a software implementation that makes the model easy to use and understand. We have also taken the opportunity to update some of the units used in the original paper, and to provide a few parameter values that were missing in the original paper. Finally, we provide an historical background to the Boron & De Weer (1976) proposal for active pH regulation and a commentary on subsequent work that has enriched our understanding of this most basic aspect of cellular physiology.

Changes in metabolic rate and N excretion in the marine invertebrateSipunculus nudusunder conditions of environmental hypercapnia

2002 ◽  
Vol 205 (8) ◽  
pp. 1153-1160 ◽  
Author(s):  
M. Langenbuch ◽  
H. O. Pörtner
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Metabolic Rate ◽  
Intracellular Ph ◽  
Energy Demand ◽  
Control Level ◽  
Ammonia Excretion ◽  
Amino Acid Catabolism ◽  
Acid Base ◽  
Selection Of

SUMMARYIncreased CO2 partial pressures (hypercapnia) as well as hypoxia are natural features of marine environments like the intertidal zone. Nevertheless little is known about the specific effects of CO2 on metabolism, except for the well-described effects on acid—base variables and regulation. Accordingly, the sediment-dwelling worm Sipunculus nudus was used as an experimental model to investigate the correlation of acid—base-induced metabolic depression and protein/amino acid catabolism, by determining the rates of oxygen consumption, ammonia excretion and O/N ratios in non-perfused preparations of body wall musculature at various levels of extra- and intracellular pH, PCO2 and [HCO3-]. A decrease in extracellular pH from control level (7.9) to 6.7 caused a reduction in aerobic metabolic rate of both normocapnic and hypercapnic tissues by 40-45 %. O/N ratios of 4.0-4.5 under control conditions indicate that amino acid catabolism meets the largest fraction of aerobic energy demand. A significant 10-15 % drop in ammonia excretion, a simultaneous reduction of O/N ratios and a transient accumulation of intracellular bicarbonate during transition to extreme acidosis suggest a reduction in net amino acid catabolism and a shift in the selection of amino acids used,favouring monoamino dicarboxylic acids and their amines (asparagine,glutamine, aspartic and glutamic acids). A drop in intracellular pH was identified as mediating this effect. In conclusion, the present data provide evidence for a regulatory role of intracellular pH in the selection of amino acids used by catabolism.

Regulation of intracellular pH in proximal tubules of avian long-looped mammalian-type nephrons

1998 ◽  
Vol 274 (6) ◽  
pp. R1526-R1535 ◽  
Author(s):  
Olga H. Brokl ◽  
Christina L. Martinez ◽  
Apichai Shuprisha ◽  
Diane E. Abbott ◽  
William H. Dantzler
Keyword(s):  
Intracellular Ph ◽  
Ph Sensitive ◽  
Fluorescent Dye ◽  
Proximal Tubules ◽  
Acid Base ◽  
Rate Of Recovery

In nonperfused proximal tubules isolated from chicken long-looped mammalian-type nephrons, intracellular pH (pHi), measured with the pH-sensitive fluorescent dye 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, was ∼7.3 under control conditions (HEPES-buffered medium with pH 7.4 at 37°C) and was reduced to ∼7.0 in response to NH4Cl pulse. The rate of recovery of pHi from this level to the resting level was 1) significantly reduced by the removal of Na+ from the bath, 2) significantly increased by the removal of Cl− from the bath, 3) unchanged by the removal of both Na+ and Cl− from the bath, 4) significantly reduced by the addition of either ethylisopropylamiloride or DIDS to the bath, 5) significantly increased by a high bath K+ concentration, and 6) unchanged by the addition of Ba2+ to the bath. These data suggest that both Na+-coupled and Cl−-coupled basolateral acid-base fluxes are involved in determining the rate of recovery of pHi after acidification. The most likely ones to be important in regulating pHi are a Na+/H+exchanger and a Na+-coupled Cl−/[Formula: see text]exchanger. In birds, long-looped mammalian-type nephrons resemble short-looped transitional nephrons but differ markedly from superficial loopless reptilian-type nephrons.

Polarity of alveolar epithelial cell acid-base permeability

2002 ◽  
Vol 282 (4) ◽  
pp. L675-L683 ◽  
Author(s):  
Dilip Joseph ◽  
Omar Tirmizi ◽  
Xiao-Ling Zhang ◽  
Edward D. Crandall ◽  
Richard L. Lubman
Keyword(s):  
Cell Membrane ◽  
Intracellular Ph ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Ph Gradient ◽  
Acid Base ◽  
Alveolar Epithelial ◽  
Basolateral Cell Membrane ◽  
Fluid Compartments ◽  
Two Fluid

We investigated acid-base permeability properties of electrically resistive monolayers of alveolar epithelial cells (AEC) grown in primary culture. AEC monolayers were grown on tissue culture-treated polycarbonate filters. Filters were mounted in a partitioned cuvette containing two fluid compartments (apical and basolateral) separated by the adherent monolayer, cells were loaded with the pH-sensitive dye 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, and intracellular pH was determined. Monolayers in HCO[Formula: see text]-free Na+ buffer (140 mM Na+, 6 mM HEPES, pH 7.4) maintained a transepithelial pH gradient between the two fluid compartments over 30 min. Replacement of apical fluid by acidic (6.4) or basic (8.0) buffer resulted in minimal changes in intracellular pH. Replacement of basolateral fluid by acidic or basic buffer resulted in transmembrane proton fluxes and intracellular acidification or alkalinization. Intracellular alkalinization was blocked ≥80% by 100 μM dimethylamiloride, an inhibitor of Na+/H+exchange, whereas acidification was not affected by a series of acid/base transport inhibitors. Additional experiments in which AEC monolayers were grown in the presence of acidic (6.4) or basic (8.0) medium revealed differential effects on bioelectric properties depending on whether extracellular pH was altered in apical or basolateral fluid compartments bathing the cells. Acid exposure reduced (and base exposure increased) short-circuit current from the basolateral side; apical exposure did not affect short-circuit current in either case. We conclude that AEC monolayers are relatively impermeable to transepithelial acid/base fluxes, primarily because of impermeability of intercellular junctions and of the apical, rather than basolateral, cell membrane. The principal basolateral acid exit pathway observed under these experimental conditions is Na+/H+ exchange, whereas proton uptake into cells occurs across the basolateral cell membrane by a different, undetermined mechanism. These results are consistent with the ability of the alveolar epithelium to maintain an apical-to-basolateral (air space-to-blood) pH gradient in situ.

scholarly journals American alligator (Alligator mississippiensis) embryos tightly regulate intracellular pH during a severe acidosis

2018 ◽  
Vol 96 (7) ◽  
pp. 723-727 ◽  
Author(s):  
R.B. Shartau ◽  
D.A. Crossley ◽  
Z.F. Kohl ◽  
R.M. Elsey ◽  
C.J. Brauner
Keyword(s):  
Intracellular Ph ◽  
Ph Regulation ◽  
Alligator Mississippiensis ◽  
American Alligator ◽  
Acid Base ◽  
Tissue Ph ◽  
Snapping Turtle ◽  
Blood Ph ◽  
Brain Ph

Crocodilian nests naturally experience high CO2 (hypercarbia), which leads to increased blood Pco2 and reduced blood pH (pHe) in embryos; their response to acid–base challenges is not known. During acute hypercarbia, snapping turtle embryos preferentially regulate tissue pH (pHi) against pHe reductions. This is proposed to be associated with CO2 tolerance in reptilian embryos and is not found in adults. In the present study, we investigated pH regulation in American alligator (Alligator mississippiensis (Daudin, 1802)) embryos exposed to 1 h of hypercarbia hypoxia (13 kPa Pco2, 9 kPa Po2). Hypercarbia hypoxia reduced pHe by 0.42 pH unit, while heart and brain pHi increased, with no change in the pHi of other tissues. The results indicate that American alligator embryos preferentially regulate pHi, similar to snapping turtle embryos, which represents a markedly different strategy of acid–base regulation than what is observed in adult reptiles. These findings suggest that preferential pHi regulation may be a strategy of acid–base regulation used by embryonic reptiles.

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