Neuronal pH Regulation: Constant Normal Intracellular pH is Maintained in Brain during Low Extracellular pH Induced by Acetazolamide—31P NMR Study

1989 ◽  
Vol 9 (3) ◽  
pp. 417-421 ◽  
Author(s):  
Sissel Vorstrup ◽  
Karl Erik Jensen ◽  
Carsten Thomsen ◽  
Ole Henriksen ◽  
Niels A. Lassen ◽  
...  
Keyword(s):  
Intracellular Ph ◽  
Ph Regulation ◽  
Extracellular Ph ◽  
Whole Body ◽  
Resonance Spectroscopy ◽  
Nmr Study ◽  
Resonance Frequencies ◽  
The Mean ◽  
Ph Decrease ◽  
Body Scanner

The intracellular pH in the brain was studied in six healthy volunteers before and immediately after the administration of 2 g of acetazolamide. Phosphorus-31 nuclear magnetic resonance spectroscopy by a 1.5 tesla whole-body scanner was used. The chemical shift between the inorganic phosphate and the phosphocreatine resonance frequencies was used for indirect assessment of the intracellular pH. The mean baseline intracellular pH was 7.05 ± 0.04 (SD). The mean pH changes obtained at 15-min intervals within the first hour of acetazolamide administration were −0.03 ± 0.04 (SD), −0.02 ± 0.03 (SD), and 0.00 ± 0.04 (SD), i.e., no statistically significant pH decrease was observed during the period where extracellular pH is known to drop markedly. Although several factors contribute to the lack of change of the intraneuronal pH, we will discuss that this observation in addition might suggest a direct intracerebral effect of acetazolamide.

19F-NMR study of primary human T lymphocyte activation: effects of mitogen on intracellular pH

1994 ◽  
Vol 266 (2) ◽  
pp. C541-C551 ◽  
Author(s):  
M. Bental ◽  
C. Deutsch
Keyword(s):  
Intracellular Ph ◽  
T Lymphocyte ◽  
Ph Regulation ◽  
Interleukin 2 ◽  
Lymphocyte Activation ◽  
Extracellular Ph ◽  
19F Nmr ◽  
Ph Values ◽  
T Lymphocyte Proliferation ◽  
Nmr Study

Intracellular pH of purified human T lymphocytes was studied using nuclear magnetic resonance (NMR) spectroscopy under physiological conditions. In this paper we introduce a new improved 19F-NMR pH probe, 2-amino-3,3'-difluoroisobutyric acid (vic-difluoro-alpha-methylalanine), which has a pKa of approximately 7.0, sensitivity of 0.83 ppm/pH, is noncytotoxic, and provides better signal-to-noise ratio for intracellular pH determinations. Quiescent and stimulated lymphocytes display different homeostatic intracellular pH values. Quiescent cells maintain intracellular pH of 7.04 +/- 0.03 at extracellular pH values between 6.9 and 7.3, and stimulated cells maintain intracellular pH of 7.25 +/- 0.05 at extracellular pH values between 7.0 and 7.5. Stimulation with ionomycin plus phorbol 12-myristate 13-acetate leads to intracellular alkalinization within 90 min, reaching the more alkaline steady-state value of 7.25 within 7-10 h. Proliferation, but not viability, of lymphocytes is dependent on extracellular pH in the range of 6.4-8.0, and this dependence is not due to limiting interleukin-2 elaboration. The mechanisms of pH regulation and the possible implications of a permissive pH for T lymphocyte proliferation are discussed.

Skeletal muscle metabolism and work capacity: a 31P-NMR study of Andean natives and lowlanders

1991 ◽  
Vol 70 (5) ◽  
pp. 1963-1976 ◽  
Author(s):  
G. O. Matheson ◽  
P. S. Allen ◽  
D. C. Ellinger ◽  
C. C. Hanstock ◽  
D. Gheorghiu ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Muscle Metabolism ◽  
Work Capacity ◽  
Calf Muscle ◽  
Whole Body ◽  
Resonance Spectroscopy ◽  
Muscle Work ◽  
Nmr Study ◽  
Nuclear Magnetic

Two metabolic features of altitude-adapted humans are the maximal O2 consumption (VO2max) paradox (higher work rates following acclimatization without increases in VO2max) and the lactate paradox (progressive reductions in muscle and blood lactate with exercise at increasing altitude). To assess underlying mechanisms, we studied six Andean Quechua Indians in La Raya, Peru (4,200 m) and at low altitude (less than 700 m) immediately upon arrival in Canada. The experimental strategy compared whole-body performance tests and single (calf) muscle work capacities in the Andeans with those in groups of sedentary, power-trained, and endurance-trained lowlanders. We used 31P nuclear magnetic resonance spectroscopy to monitor noninvasively changes in concentrations of phosphocreatine [( PCr]), [Pi], [ATP], [PCr]/[PCr] + creatine ([Cr]), [Pi]/[PCr] + [Cr], and pH in the gastrocnemius muscle of subjects exercising to fatigue. Our results indicate that the Andeans 1) are phenotypically unique with respect to measures of anaerobic and aerobic work capacity, 2) despite significantly lower anaerobic capacities, are capable of calf muscle work rates equal to those of highly trained power- and endurance-trained athletes, and 3) compared with endurance-trained athletes with significantly higher VO2max values and power-trained athletes with similar VO2max values, display, respectively, similar and reduced perturbation of all parameters related to the phosphorylation potential and to measurements of [Pi], [PCr], [ATP], and muscle pH derivable from nuclear magnetic resonance. Because the lactate paradox may be explained on the basis of tighter ATP demand-supplying coupling, we postulate that a similar mechanism may explain 1) the high calf muscle work capacities in the Andeans relative to measures of whole-body work capacity, 2) the VO2max paradox, and 3) anecdotal reports of exceptional work capacities in indigenous altitude natives.

scholarly journals The Influence of Age on pH Regulation in Hippocampal Slices Before, During, and after Anoxia

1997 ◽  
Vol 17 (5) ◽  
pp. 560-566 ◽  
Author(s):  
Eugene L. Roberts ◽  
Ching-Ping Chih
Keyword(s):  
Brain Tissue ◽  
Intracellular Ph ◽  
Ph Regulation ◽  
Hippocampal Slices ◽  
Extracellular Ph ◽  
Aged Brain ◽  
Age Related ◽  
Anoxic Depolarization ◽  
Rate Of Recovery ◽  
Old Rats

Changes in intracellular and extracellular pH may influence the vulnerability of brain tissue to anoxic or ischemic damage. In the present study, we investigated whether the increased vulnerability of aged brain tissue to anoxic damage is associated with age-related alterations in pH regulation. We obtained evidence for altered pH regulation by measuring concurrent changes in intracellular and extracellular pH before, during, and after anoxia in hippocampal slices from young adult (6–8 months old) and aged (24–27 months old) rats. We found indications of impaired pH regulation in aged hippocampal slices (a) before anoxia, as seen in a lower resting intracellular pH, (b) during anoxia, as seen in a slower decline in extracellular pH, and (c) during recovery after anoxia, as seen in a slower rate of recovery of intracellular pH. Age-related changes in pH regulation may contribute to the faster onset of anoxic depolarization in aged brain tissue during anoxia.

scholarly journals Myocardial intracellular pH in a perfused rainbow trout heart during extracellular acidosis in the presence and absence of adrenaline

1986 ◽  
Vol 125 (1) ◽  
pp. 347-359 ◽  
Author(s):  
A. P. Farrell ◽  
C. L. Milligan
Keyword(s):  
Rainbow Trout ◽  
Intracellular Ph ◽  
Ph Regulation ◽  
Respiratory Acidosis ◽  
Mechanical Efficiency ◽  
Extracellular Ph ◽  
Salmo Gairdneri ◽  
Intracellular Ph Regulation ◽  
Extracellular Acidosis

Myocardial intracellular pH was measured in a perfused rainbow trout, Salmo gairdneri, with DMO (5,5-dimethyl-2,4-oxazlidinedione), to test the hypothesis that catecholamines promote active regulation of myocardial pH in order to protect contractility during a respiratory acidosis comparable to that observed after exercise. Under control conditions (extracellular pH = 8.0; PCO2 = 2 Torr), myocardial pH was 7.53 +/− 0.01 (N = 5). Acidosis (extracellular pH = 7.45; PCO2 = 8.6 Torr) reduced contractility, mechanical efficiency and intracellular pH (7.25 +/− 0.04), but did not affect myocardial O2 consumption. The addition of 0.5 mumol l-1 adrenaline during extracellular acidosis prevented the loss of contractility, restored mechanical efficiency, but did not change intracellular pH significantly. Thus, adrenaline enabled cardiac contractility to recover, without intracellular pH regulation, possibly by modulation of sarcolemmal calcium changes. The absence of a myocardial acidosis after exercise in vivo is discussed with respect to possible intracellular pH regulation via lactate uptake and metabolism.

scholarly journals Glia modulation of the extracellular milieu as a factor in central CO2 chemosensitivity and respiratory control

2010 ◽  
Vol 108 (6) ◽  
pp. 1803-1811 ◽  
Author(s):  
Joseph S. Erlichman ◽  
J. C. Leiter
Keyword(s):  
Gap Junctions ◽  
Intracellular Ph ◽  
Ph Regulation ◽  
Extracellular Fluid ◽  
Respiratory Control ◽  
Extracellular Ph ◽  
Bicarbonate Transport ◽  
Lactate Shuttle ◽  
Central Chemosensitivity ◽  
Intracellular Ph Regulation

We discuss the influence of astrocytes on respiratory function, particularly central CO2 chemosensitivity. Fluorocitrate (FC) poisons astrocytes, and studies in intact animals using FC provide strong evidence that disrupting astrocytic function can influence CO2 chemosensitivity and ventilation. Gap junctions interconnect astrocytes and contribute to K+ homeostasis in the extracellular fluid (ECF). Blocking gap junctions alters respiratory control, but proof that this is truly an astrocytic effect is lacking. Intracellular pH regulation of astrocytes has reciprocal effects on extracellular pH. Electrogenic sodium-bicarbonate transport (NBCe) is present in astrocytes. The activity of NBCe alkalinizes intracellular pH and acidifies extracellular pH when activated by depolarization (and a subset of astrocytes are depolarized by hypercapnia). Thus, to the extent that astrocytic intracellular pH regulation during hypercapnia lowers extracellular pH, astrocytes will amplify the hypercapnic stimulus and may influence central chemosensitivity. However, the data so far provide only inferential support for this hypothesis. A lactate shuttle from astrocytes to neurons seems to be active in the retrotrapezoid nucleus (RTN) and important in setting the chemosensory stimulus in the RTN (and possibly other chemosensory nuclei). Thus astrocytic processes, so vital in controlling the constituents of the ECF in the central nervous system, may profoundly influence central CO2 chemosensitivity and respiratory control.

Metabolic response to halothane in piglets susceptible to malignant hyperthermia: an in vivo 31P-NMR study

1993 ◽  
Vol 75 (2) ◽  
pp. 955-962 ◽  
Author(s):  
C. Decanniere ◽  
P. Van Hecke ◽  
F. Vanstapel ◽  
H. Ville ◽  
R. Geers
Keyword(s):  
Malignant Hyperthermia ◽  
Intracellular Ph ◽  
Metabolic Response ◽  
Stress Test ◽  
Recovery Period ◽  
Muscle Metabolism ◽  
Resonance Spectroscopy ◽  
Intracellular Acidosis ◽  
Nmr Study

Using in vivo 31P-nuclear magnetic resonance spectroscopy, we studied the skeletal muscle metabolism of 17 anesthetized malignant hyperthermia-susceptible piglets and 25 control piglets during and after a halothane stress test. At rest, the phosphocreatine- (PCr) to-ATP ratio was 12% higher in the anesthetized piglets than in the control piglets, which may reflect a higher proportion of fast glycolytic fibers in the former. About 15 min of halothane administration sufficed to provoke onset of a reaction, which was characterized by a reciprocal drop in PCr and an increase in Pi with commencing intracellular acidosis. Halothane was withdrawn after a 20% drop in PCr. Within the next few minutes, intracellular pH dropped sharply and phosphomonoesters (PME) accumulated excessively. ATP was observed to decrease in 8 of the 17 animals. Halothane inhalation provoked a switch of metabolism toward glycolysis. Accumulation of PME suggests a mismatch between glycogenolysis and glycolysis. Despite severe acidification, glycolysis was not completely halted. Recovery of PCr and Pi started approximately 5 min after halothane withdrawal, with a longer time constant for recovery of the former. PME and intracellular pH aberrations lingered and started to recover later. Lost ATP was never restored within the observed recovery period of approximately 20 min.

Ischemic contracture begins when anaerobic glycolysis stops: a 31P-NMR study of isolated rat hearts

1991 ◽  
Vol 261 (2) ◽  
pp. H469-H478 ◽  
Author(s):  
P. B. Kingsley ◽  
E. Y. Sako ◽  
M. Q. Yang ◽  
S. D. Zimmer ◽  
K. Ugurbil ◽  
...  
Keyword(s):  
Intracellular Ph ◽  
Left Ventricular ◽  
Atp Depletion ◽  
Resonance Spectroscopy ◽  
Anaerobic Glycolysis ◽  
Ischemic Contracture ◽  
Atp Levels ◽  
Nmr Study ◽  
Rat Hearts ◽  
Glycolytic Atp

The relationships among myocardial ATP, intracellular pH, and ischemic contracture in Langendorff-perfused rat hearts were investigated by 31P nuclear magnetic resonance spectroscopy during total global normothermic ischemia while the left ventricular pressure was recorded continuously via an intraventricular balloon. Glucose-perfused hearts (n = 63) were divided into five groups based on the time of onset of contracture (TOC), and three other groups of hearts were treated to vary the ischemic glycogen availability. ATP levels, which showed no evidence of accelerated ATP depletion during contracture, were significant and variable at TOC. Intracellular pH initially declined and then leveled off at TOC, with lower final pH in hearts with later TOC. We conclude that contracture began when anaerobic glycolysis (and thus glycolytic ATP synthesis) stopped. These results, though consistent with the concept that ischemic contracture in normal hearts results from rigor bond formation due to low ATP levels at the myofibrils, suggest that TOC is more closely related to glycolytic ATP production than to total cellular ATP content, thus providing evidence of some degree of subcellular compartmentation or metabolite channeling. In glycolytically inhibited hearts, the quite early contracture may have a Ca2+ component.

Effects of Metabolic Alkalosis, Metabolic Acidosis and Uraemia on Whole-Body Intracellular pH in Man

1977 ◽  
Vol 52 (2) ◽  
pp. 125-135 ◽  
Author(s):  
A. Tizianello ◽  
G. De Ferrari ◽  
G. Gurreri ◽  
N. Acquarone
Keyword(s):  
Metabolic Acidosis ◽  
Intracellular Ph ◽  
Metabolic Alkalosis ◽  
Buffer Capacity ◽  
Normal Subjects ◽  
Extracellular Ph ◽  
Whole Body ◽  
Cellular Environment ◽  
Acid Load ◽  
Acute Metabolic Acidosis

1. Whole-body intracellular pH (pH1) was measured by the 14C-labelled DMO method in twenty-four control subjects, eighteen normal subjects with induced acute metabolic alkalosis, ten normal subjects with induced acute metabolic acidosis, twelve normal subjects with chronic acidosis and in fifteen patients with chronic renal insufficiency and acidosis. 2. The change in pH1 per unit change in extracellular pH is significantly larger in acute metabolic alkalosis than in acute metabolic acidosis. In chronic metabolic acidosis, pH1 decreased in proportion to the total amount of ammonium chloride administered; pH1 was normal in patients with uraemic acidosis. 3. These observations confirm the role that tissue buffers play in the protection of the cellular environment in some forms of acidosis. When the acid load overwhelms tissue buffer capacity, pH1 becomes a function of extracellular pH. 4. Cells seem more protected from acute acidosis than from acute alkalosis.

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