Intersubject differences in the effect of acidosis on phosphocreatine recovery kinetics in muscle after exercise are due to differences in proton efflux rates

2007 ◽  
Vol 293 (1) ◽  
pp. C228-C237 ◽  
Author(s):  
Nicole M. A. van den Broek ◽  
Henk M. M. L. De Feyter ◽  
Larry de Graaf ◽  
Klaas Nicolay ◽  
Jeanine J. Prompers
Keyword(s):  
Ph Dependence ◽  
Resonance Spectroscopy ◽  
Muscle Exercise ◽  
Intracellular Acidosis ◽  
Proton Efflux ◽  
Efflux Rate ◽  
Cytosolic Ph ◽  
Efflux Rate Constant ◽  
And Control ◽  
Kinetics Of

31P magnetic resonance spectroscopy provides the possibility of obtaining bioenergetic data during skeletal muscle exercise and recovery. The time constant of phosphocreatine (PCr) recovery (τPCr) has been used as a measure of mitochondrial function. However, cytosolic pH has a strong influence on the kinetics of PCr recovery, and it has been suggested that τPCr should be normalized for end-exercise pH. A general correction can only be applied if there are no intersubject differences in the pH dependence of τPCr. We investigated the pH dependence of τPCr on a subject-by-subject basis. Furthermore, we determined the kinetics of proton efflux at the start of recovery. Intracellular acidosis slowed PCr recovery, and the pH dependence of τPCr differed among subjects, ranging from −33.0 to −75.3 s/pH unit. The slope of the relation between τPCr and end-exercise pH was positively correlated with both the proton efflux rate and the apparent proton efflux rate constant, indicating that subjects with a smaller pH dependence of τPCr have a higher proton efflux rate. Our study implies that simply correcting τPCr for end-exercise pH is not adequate, in particular when comparing patients and control subjects, because certain disorders are characterized by altered proton efflux from muscle fibers.

Kinetic modelling of processes in the cholinergic synapse. Mechanisms of functioning and control methods

2020 ◽  
pp. 121-133
Author(s):  
Sergey Varfolomeev ◽  
Viktor Bykov ◽  
Svetlana Tsybenova
Keyword(s):  
Kinetic Model ◽  
Kinetic Modelling ◽  
Ph Dependence ◽  
Synaptic Cleft ◽  
Cholinergic Synapse ◽  
Physico Chemical ◽  
And Control ◽  
Kinetics Of ◽  
And Diffusion ◽  
Neuromuscular Paralysis

The kinetic model describing the dynamics of synaptic “discharge” taking into account the kinetics of the injection of the neurotransmitter into the synaptic cleft, the pH-dependence of catalytic activity of the enzyme and diffusion withdrawal of protons is proposed and studied. In the framework of the kinetic model, the functioning of the cholinergic synapse is considered. The results of mathematical modeling of changes in the level of acetylcholine, induced pH impulse, the influence of the frequency of impulse transfer and inhibition of acetylcholinesterase are presented. Physico-chemical explanation for a number of important physiological phenomena, such as neuromuscular paralysis, the molecular mechanism of neurological memory, actions of nerve poisons and toxins and Alzheimer’s disease is given.

Kinetic modelling of processes in the cholinergic synapse. Mechanisms of functioning and control methods

2020 ◽  
pp. 127-139
Author(s):  
Sergey Varfolomeev ◽  
Viktor Bykov ◽  
Svetlana Tsybenova
Keyword(s):  
Kinetic Model ◽  
Kinetic Modelling ◽  
Ph Dependence ◽  
Synaptic Cleft ◽  
Cholinergic Synapse ◽  
Physico Chemical ◽  
And Control ◽  
Kinetics Of ◽  
And Diffusion ◽  
Neuromuscular Paralysis

The kinetic model describing the dynamics of synaptic “discharge” taking into account the kinetics of the injection of the neurotransmitter into the synaptic cleft, the pH-dependence of catalytic activity of the enzyme and diffusion withdrawal of protons is proposed and studied. In the framework of the kinetic model, the functioning of the cholinergic synapse is considered. The results of mathematical modeling of changes in the level of acetylcholine, induced pH impulse, the influence of the frequency of impulse transfer and inhibition of acetylcholinesterase are presented. Physico-chemical explanation for a number of important physiological phenomena, such as neuromuscular paralysis, the molecular mechanism of neurological memory, actions of nerve poisons and toxins and Alzheimer’s disease is given.

Regulation of intracellular pH in the perfused heart by external HCO3- and Na(+)-H+ exchange

1993 ◽  
Vol 265 (1) ◽  
pp. H289-H298 ◽  
Author(s):  
A. A. Grace ◽  
H. L. Kirschenlohr ◽  
J. C. Metcalfe ◽  
G. A. Smith ◽  
P. L. Weissberg ◽  
...  
Keyword(s):  
Intracellular Ph ◽  
Cardiac Tissue ◽  
Intracellular Acidosis ◽  
Proton Efflux ◽  
Efflux Rate ◽  
Perfused Heart ◽  
Acid Load ◽  
Ethanesulfonic Acid ◽  
Intracellular Buffering Capacity ◽  
Ferret Heart

Both Na(+)-dependent HCO3- influx and the Na(+)-H+ antiport have been shown to contribute to recovery from intracellular acidosis in avian and mammalian cardiac tissue. We have investigated the participation of these mechanisms in the recovery of intracellular pH (pHi) after an acid load in the Langendorff-perfused ferret heart. pHi was measured from the phosphorus-31 nuclear magnetic resonance chemical shift of 2-deoxy-D-glucose 6-phosphate. Basal pHi was higher in HCO(3-)-buffered solution (7.05 +/- 0.01; n = 8) than in nominally HCO(3-)-free N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) solution (6.98 +/- 0.02; n = 9). Addition of 5-(N-ethyl-N-isopropyl)amiloride (EIPA) caused a significant fall in pHi in HEPES solution (6.91 +/- 0.02; n = 5) but not in HCO3- solution (7.02 +/- 0.02; n = 5). Intrinsic intracellular buffering capacity in 0 Na(+)-HEPES solution was 37 +/- 2 mmol/l (n = 4), and additional buffering due to HCO(3-)-CO2 was approximately 13 mmol/l in HCO3- solution. After an intracellular acidosis induced by an NH4Cl prepulse, the proton efflux rate (JH) at pHi 6.90 was 0.5 +/- 0.2 nmol.l-1.min-1 (n = 14) in HEPES solution and 1.2 +/- 0.4 mmol.l-1.min-1 (n = 13) in HCO3- solution. The addition of 1 microM EIPA effectively blocked proton efflux in HEPES solution (JH < 0.1 mmol.l-1.min-1; n = 8), whereas it slowed pHi recovery in HCO3- solution (JH = 0.6 +/- 0.2 mmol.l-1.min-1; n = 9). There was no recovery of pHi in Na(+)-free HCO3- solution (JH < 0.1 mmol.l-1.min-1; n = 3). The Na(+)-H+ antiport and a mechanism requiring both external Na+ and HCO3- each contribute approximately 50% to proton efflux at pHi 6.90 during the recovery from intracellular acidosis in the isolated perfused mammalian heart.

Triiodothyronine-induced changes in proton efflux from rat skeletal muscle in vivo

1995 ◽  
Vol 133 (2) ◽  
pp. 260-264 ◽  
Author(s):  
Campbell H Thompson ◽  
Graham J Kemp ◽  
George K Radda
Keyword(s):  
Skeletal Muscle ◽  
Magnetic Resonance ◽  
Transport Processes ◽  
Resonance Spectroscopy ◽  
Rat Skeletal Muscle ◽  
Proton Efflux ◽  
Efflux Rate ◽  
Ph Change ◽  
Induced Changes

Thompson CH, Kemp GJ, Radda GK. Triiodothyronine-induced changes in proton efflux from rat skeletal muscle in vivo. Eur J Endocrinol 1995;133:260–4. ISSN 0804–4643 Hyperthyroidism is associated with muscle weakness, abnormal aerobic metabolism and increased lactate production. Muscle cell acidification during exercise is reduced, suggesting abnormally increased proton efflux. Using 31P magnetic resonance spectroscopy to measure cell pH and phosphocreatine concentration, we quantified effective proton efflux from rat leg muscle in vivo following 10-Hz sciatic nerve stimulation in seven rats injected with triiodothyronine (T3) for 5 days and in 11 controls. Proton efflux during recovery was sigmoidally pH-dependent in both groups but the initial proton efflux rate did not differ (16 ± 3 mmol·kg−1 · min−1 in treated animals vs 15 ± 1 mmol·kg−1·min−1 in controls), despite a significantly smaller pH change from basal in treated animals (0.60 ± 0.04 vs 0.78 ± 0.03 in controls, p = 0.002). The pH dependence of proton efflux can be characterized by an apparent Km, defined as the pH below basal at which proton efflux rate falls to half its start-of-recovery value. This Km was smaller in the T3-treated group (0.44 ± 0.04 vs 0.59 ± 0.03 in controls, p = 0.02). This suggests an increased affinity for protons by cell membrane proton transport processes such as the sodium–proton antiporter and may explain some of the metabolic changes seen clinically in hyperthyroid skeletal muscle. CH Thompson, MRC Biochemical and Clinical Magnetic Resonance Unit, Oxford Radcliffe Hospital Trust, Headington, Oxford OX3 9DU, UK

Investigation of irradiation-induced nucleation processes in silicon and germanium

1995 ◽  
Vol 53 ◽  
pp. 224-225
Author(s):  
Harry A. Atwater ◽  
C.M. Yang ◽  
K.V. Shcheglov
Keyword(s):  
Room Temperature ◽  
Crystal Size ◽  
Initial Distribution ◽  
Engineering Control ◽  
Size Evolution ◽  
Silicon And Germanium ◽  
Ge Quantum Dot ◽  
And Control ◽  
Germanium Quantum Dots ◽  
Kinetics Of

Studies of the initial stages of nucleation of silicon and germanium have yielded insights that point the way to achievement of engineering control over crystal size evolution at the nanometer scale. In addition to their importance in understanding fundamental issues in nucleation, these studies are relevant to efforts to (i) control the size distributions of silicon and germanium “quantum dots𠇍, which will in turn enable control of the optical properties of these materials, (ii) and control the kinetics of crystallization of amorphous silicon and germanium films on amorphous insulating substrates so as to, e.g., produce crystalline grains of essentially arbitrary size.Ge quantum dot nanocrystals with average sizes between 2 nm and 9 nm were formed by room temperature ion implantation into SiO2, followed by precipitation during thermal anneals at temperatures between 30°C and 1200°C[1]. Surprisingly, it was found that Ge nanocrystal nucleation occurs at room temperature as shown in Fig. 1, and that subsequent microstructural evolution occurred via coarsening of the initial distribution.

scholarly journals Tuning flavin environment to detect and control light-induced conformational switching in Drosophila cryptochrome

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Siddarth Chandrasekaran ◽  
Connor M. Schneps ◽  
Robert Dunleavy ◽  
Changfan Lin ◽  
Cristina C. DeOliveira ◽  
...  
Keyword(s):  
Side Reactions ◽  
Resonance Spectroscopy ◽  
Conformational Switching ◽  
Spin Resonance ◽  
Degradation Activity ◽  
Recognition Motifs ◽  
Cellular Turnover ◽  
Control Light ◽  
Dynamics Simulations ◽  
And Control

AbstractLight-induction of an anionic semiquinone (SQ) flavin radical in Drosophila cryptochrome (dCRY) alters the dCRY conformation to promote binding and degradation of the circadian clock protein Timeless (TIM). Specific peptide ligation with sortase A attaches a nitroxide spin-probe to the dCRY C-terminal tail (CTT) while avoiding deleterious side reactions. Pulse dipolar electron-spin resonance spectroscopy from the CTT nitroxide to the SQ shows that flavin photoreduction shifts the CTT ~1 nm and increases its motion, without causing full displacement from the protein. dCRY engineered to form the neutral SQ serves as a dark-state proxy to reveal that the CTT remains docked when the flavin ring is reduced but uncharged. Substitutions of flavin-proximal His378 promote CTT undocking in the dark or diminish undocking in the light, consistent with molecular dynamics simulations and TIM degradation activity. The His378 variants inform on recognition motifs for dCRY cellular turnover and strategies for developing optogenetic tools.

scholarly journals Hydrogen exchange kinetics of human hemoglobins. The pH dependence of solvent accessibility in cyanomet-, oxy-, and deoxyhemoglobin.

1978 ◽  
Vol 253 (10) ◽  
pp. 3702-3707
Author(s):  
B.E. Hedlund ◽  
P.E. Hallaway ◽  
B.E. Hallaway ◽  
E.S. Benson ◽  
A. Rosenberg
Keyword(s):  
Hydrogen Exchange ◽  
Solvent Accessibility ◽  
Ph Dependence ◽  
Exchange Kinetics ◽  
Kinetics Of

scholarly journals Striatal glutamate and the conversion to psychosis: a prospective 1H-MRS imaging study

2012 ◽  
Vol 16 (2) ◽  
pp. 471-475 ◽  
Author(s):  
Camilo de la Fuente-Sandoval ◽  
Pablo León-Ortiz ◽  
Mariana Azcárraga ◽  
Rafael Favila ◽  
Sylvana Stephano ◽  
...  
Keyword(s):  
Proton Magnetic Resonance ◽  
Proton Magnetic Resonance Spectroscopy ◽  
Imaging Study ◽  
Psychotic Symptoms ◽  
Resonance Spectroscopy ◽  
Control Groups ◽  
1H Mrs ◽  
Ultra High Risk ◽  
And Control

Abstract Increased glutamate levels in the associative-striatum have been described in subjects at ultra-high risk for psychosis (UHR); nevertheless, it is unclear whether this abnormality predicts the conversion to psychosis. Nineteen subjects at UHR and 26 controls were studied using proton magnetic resonance spectroscopy. Subjects at UHR were clinically followed for 2 yr. Seven UHR subjects (37%) transitioned to a psychotic disorder and the remaining 12 did not exhibit psychotic symptoms at the most recent follow-up. The psychosis transition group had higher glutamate levels compared to both non-transition and control groups (p = 0.02 and p < 0.01, respectively; effect size 1.39). These pilot findings suggest that the conversion to psychosis is associated with increased glutamate levels in the associative-striatum.

Magnetic resonance spectroscopy of high-energy phosphates and lactate immediately after coronary artery bypass surgery

Perfusion ◽  
1998 ◽  
Vol 13 (5) ◽  
pp. 328-333 ◽  
Author(s):  
D NF Harris ◽  
J A Wilson ◽  
S D Taylor-Robinson ◽  
K M Taylor
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Cerebral Ischaemia ◽  
Artery Bypass ◽  
High Energy ◽  
Jugular Bulb ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
Intracellular Acidosis ◽  
High Incidence

Hypothermic cardiopulmonary bypass (CPB) is associated with a high incidence of neuropsychological defects, marked cerebral swelling immediately after surgery and jugular bulb desaturation during rewarming. This suggests cerebral ischaemia may occur, but evidence is indirect. We studied four patients with 31P magnetic resonance spectroscopy (MRS) and four with 1H MRS before and immediately after coronary surgery. There was no visible lactate in 1H MR spectra. In 31P MR spectra, the ratio of phosphocreatine to adenosine triphosphate was maintained (before: 2.13 ± 0.86 vs after: 2.57 ± 1.31; mean ± 1 SD) and there was no intracellular acidosis (intracellular pH: 7.1 ± 0.04 vs 7.16 ± 0.08), while phosphocreatine/inorganic phosphate was increased immediately after the operation (2.92 ± 0.37 vs 6.39 ± 2.67, p = 0.03). This suggests rebound replacement of energy stores following recovery from temporary cerebral ischaemia during CPB: intra-operative studies would be needed to test this hypothesis further.

scholarly journals Identification of Tyr residues that enhance folate substrate binding and constrain oscillation of the proton-coupled folate transporter (PCFT-SLC46A1)

2015 ◽  
Vol 308 (8) ◽  
pp. C631-C641 ◽  
Author(s):  
Michele Visentin ◽  
Ersin Selcuk Unal ◽  
Mitra Najmi ◽  
Andras Fiser ◽  
Rongbao Zhao ◽  
...  
Keyword(s):  
Choroid Plexus ◽  
Rate Constant ◽  
Binding Pocket ◽  
Wild Type ◽  
Efflux Rate ◽  
High Affinity ◽  
Extracellular Compartment ◽  
Efflux Rate Constant ◽  
Opposite Compartment

The proton-coupled folate transporter (PCFT) mediates intestinal folate absorption and transport of folates across the choroid plexus. This study focuses on the role of Tyr residues in PCFT function. The substituted Cys-accessibility method identified four Tyr residues (Y291, Y362, Y315, and Y414) that are accessible to the extracellular compartment; three of these (Y291, Y362, and Y315) are located within or near the folate binding pocket. When the Tyr residues were replaced with Cys or Ala, these mutants showed similar (up to 6-fold) increases in influx Vmax and Kt/ Ki for [3H]methotrexate and [3H]pemetrexed. When the Tyr residues were replaced with Phe, these changes were moderated or absent. When Y315A PCFT was used as representative of the mutants and [3H]pemetrexed as the transport substrate, this substitution did not increase the efflux rate constant. Furthermore, neither influx nor efflux mediated by Y315A PCFT was transstimulated by the presence of substrate in the opposite compartment; however, substantial bidirectional transstimulation of transport was mediated by wild-type PCFT. This resulted in a threefold greater efflux rate constant for cells that express wild-type PCFT than for cells that express Y315 PCFT under exchange conditions. These data suggest that these Tyr residues, possibly through their rigid side chains, secure the carrier in a high-affinity state for its folate substrates. However, this may be achieved at the expense of constraining the carrier's mobility, thereby decreasing the rate at which the protein oscillates between its conformational states. The Vmax generated by these Tyr mutants may be so rapid that further augmentation during transstimulation may not be possible.

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