scholarly journals Correlation of cardiac performance with cellular energetic components in the oxygen-deprived turtle heart

2009 ◽  
Vol 297 (3) ◽  
pp. R756-R768 ◽  
Author(s):  
Jonathan A. W. Stecyk ◽  
Christian Bock ◽  
Johannes Overgaard ◽  
Tobias Wang ◽  
Anthony P. Farrell ◽  
...  
Keyword(s):  
Free Energy ◽  
Atp Hydrolysis ◽  
Fold Increase ◽  
High Energy ◽  
Cardiac Performance ◽  
Freshwater Turtle ◽  
Energy Status ◽  
Autonomic Cardiac Regulation

The relationship between cardiac energy metabolism and the depression of myocardial performance during oxygen deprivation has remained enigmatic. Here, we combine in vivo 31P-NMR spectroscopy and MRI to provide the first temporal profile of in vivo cardiac energetics and cardiac performance of an anoxia-tolerant vertebrate, the freshwater turtle ( Trachemys scripta) during long-term anoxia exposure (∼3 h at 21°C and 11 days at 5°C). During anoxia, phosphocreatine (PCr), unbound levels of inorganic phosphate (effective P i2−), intracellular pH (pH i), and free energy of ATP hydrolysis (dG/dξ) exhibited asymptotic patterns of change, indicating that turtle myocardial high-energy phosphate metabolism and energetic state are reset to new, reduced steady states during long-term anoxia exposure. At 21°C, anoxia caused a reduction in pH i from 7.40 to 7.01, a 69% decrease in PCr and a doubling of effective P i2−. ATP content remained unchanged, but the free energy of ATP hydrolysis (dG/dξ) decreased from −59.6 to −52.5 kJ/mol. Even so, none of these cellular changes correlated with the anoxic depression of cardiac performance, suggesting that autonomic cardiac regulation may override putative cellular feedback mechanisms. In contrast, during anoxia at 5°C, when autonomic cardiac control is severely blunted, the decrease of pH i from 7.66 to 7.12, 1.9-fold increase of effective P i2−, and 6.4 kJ/mol decrease of dG/dξ from −53.8 to −47.4 kJ/mol were significantly correlated to the anoxic depression of cardiac performance. Our results provide the first evidence for a close, long-term coordination of functional cardiac changes with cellular energy status in a vertebrate, with a potential for autonomic control to override these immediate relationships.

Metabolic and energy correlates of intracellular pH in progressive fatigue of squid (L. brevis) mantle muscle

1996 ◽  
Vol 271 (5) ◽  
pp. R1403-R1414 ◽  
Author(s):  
H. O. Portner ◽  
E. Finke ◽  
P. G. Lee
Keyword(s):  
Free Energy ◽  
Critical Velocity ◽  
Energy Levels ◽  
High Energy ◽  
Swimming Velocity ◽  
High Energy Phosphates ◽  
Energy Status ◽  
Intracellular Acidosis ◽  
Model Calculations

Squid (Lolliguncula brevis) were exercised at increasing swimming speeds to allow us to analyze the correlated changes in intracellular metabolic, acid-base, and energy status of the mantle musculature. Beyond a critical swimming velocity of 1.5 mantle lengths/s, an intracellular acidosis developed that was caused by an initial base loss from the cells, the onset of respiratory acidification, and, predominantly, octopine formation. The acidosis was correlated with decreasing levels of phospho-L-arginine and, thus, supported ATP buffering at the expense of the phosphagen. Monohydrogenphosphate, the actual substrate of glycogen phosphorylase accumulated, enabling glycogen degradation, despite progressive acidosis. In addition to octopine, succinate, and glycerophosphate accumulation, the onset of acidosis characterizes the critical velocity and indicates the transition to a non-steady-state time-limited situation. Accordingly, swimming above the critical velocity caused cellular energy levels (in vivo Gibbs free energy change of ATP hydrolysis) to fall. A minimal value was reached at about -45 kJ/mol. Model calculations demonstrate that changes in free Mg2+ levels only minimally affect ATP free energy, but minimum levels are relevant in maintaining functional concentrations of Mg(2+)-complexed adenylates. Model calculations also reveal that phosphagen breakdown enabled L. brevis to reach swimming speeds about three times higher than the critical velocity. Comparison of two offshore squid species (Loligo pealei and Illex illecebrosus) with the estuarine squid L.brevis indicates that the latter uses a strategy to delay the exploitation of high-energy phosphates and protect energy levels at higher than the minimum levels (-42 kJ/mol) characterizing fatigue in the other species. A more economical use of anaerobic resources and an early reduction in performance may enable L. brevis to tolerate more extreme environmental conditions in shallow estuarine waters and even hypoxic environments and to prevent a fatal depletion of energy stores.

scholarly journals The Middle Domain of Hsp90 Acts as a Discriminator between Different Types of Client Proteins

2006 ◽  
Vol 26 (22) ◽  
pp. 8385-8395 ◽  
Author(s):  
Patricija Hawle ◽  
Martin Siepmann ◽  
Anja Harst ◽  
Marco Siderius ◽  
H. Peter Reusch ◽  
...  
Keyword(s):  
Atp Hydrolysis ◽  
Mutational Analysis ◽  
Fold Increase ◽  
Cellular Protein ◽  
Hydrolysis Rate ◽  
Cellular Activity ◽  
Protein Levels ◽  
Middle Domain ◽  
Client Proteins

ABSTRACT The mechanism of client protein activation by Hsp90 is enigmatic, and it is uncertain whether Hsp90 employs a common route for all proteins. Using a mutational analysis approach, we investigated the activation of two types of client proteins, glucocorticoid receptor (GR) and the kinase v-Src by the middle domain of Hsp90 (Hsp90M) in vivo. Remarkably, the overall cellular activity of v-Src was highly elevated in a W300A mutant yeast strain due to a 10-fold increase in cellular protein levels of the kinase. In contrast, the cellular activity of GR remained almost unaffected by the W300A mutation but was dramatically sensitive to S485Y and T525I exchanges. In addition, we show that mutations S485Y and T525I in Hsp90M reduce the ATP hydrolysis rate, suggesting that Hsp90 ATPase is more tightly regulated than assumed previously. Therefore, the activation of GR and v-Src has various demands on Hsp90 biochemistry and is dependent on separate functional regions of Hsp90M. Thus, Hsp90M seems to discriminate between different substrate types and to adjust the molecular chaperone for proper substrate activation.

scholarly journals Studies of the long-term regulation of hepatic pyruvate dehydrogenase kinase

1998 ◽  
Vol 329 (1) ◽  
pp. 89-94 ◽  
Author(s):  
C. Mary SUGDEN ◽  
G. D. Lee FRYER ◽  
A. Karen ORFALI ◽  
A. David PRIESTMAN ◽  
Elaine DONALD ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Pyruvate Dehydrogenase ◽  
Unsaturated Fatty Acids ◽  
Fold Increase ◽  
Membrane Lipid ◽  
Dietary Lipid ◽  
Pyruvate Dehydrogenase Kinase ◽  
Plasma Insulin Concentration

The administration of a low-carbohydrate/high-saturated-fat (LC/HF) diet for 28 days or starvation for 48 h both increased pyruvate dehydrogenase kinase (PDHK) activity in extracts of rat hepatic mitochondria, by approx. 2.1-fold and 3.5-fold respectively. ELISAs of extracts of hepatic mitochondria, conducted over a range of pyruvate dehydrogenase (PDH) activities, revealed that mitochondrial immunoreactive PDHKII (the major PDHK isoform in rat liver) was significantly increased by approx. 1.4-fold after 28 days of LC/HF feeding and by approx. 2-fold after 48 h of starvation. The effect of LC/HF feeding to increase hepatic PDHK activity was retained through hepatocyte preparation, but was decreased on 21 h culture with insulin (100μ-i.u./ml). A sustained (24 h) 2-4-fold elevation in plasma insulin concentration in vivo (achieved by insulin infusion via an osmotic pump) suppressed the effect of LC/HF feeding so that hepatic PDHK activities did not differ significantly from those of (insulin-infused) control rats. The increase in hepatic PDHK activity evoked by 28 days of LC/HF feeding was prevented and reversed (within 24 h) by the replacement of 7% of the dietary lipid with long-chain ω-3 fatty acids. Analysis of hepatic membrane lipid revealed a 1.9-fold increase in the ratio of total polyunsaturated ω-3 fatty acids to total mono-unsaturated fatty acids. The results indicate that the increased hepatic PDHK activities observed in livers of LC/HF-fed or 48 h-starved rats are associated with long-term actions to increase hepatic PDHKII concentrations. The long-term regulation of hepatic PDHK by LC/HF feeding might be achieved through an impaired action of insulin to suppress PDHK activity. In addition, the fatty acid composition of the diet, rather than the fat content, is a key influence.

scholarly journals Effect of muscle action and metabolic strain on oxidative metabolic responses in human skeletal muscle

1999 ◽  
Vol 87 (5) ◽  
pp. 1768-1775 ◽  
Author(s):  
C. A. Combs ◽  
A. H. Aletras ◽  
R. S. Balaban
Keyword(s):  
Free Energy ◽  
Atp Hydrolysis ◽  
Tibialis Anterior Muscle ◽  
Respiratory Control ◽  
Oxidative Capacity ◽  
Resonance Spectroscopy ◽  
Muscle Action ◽  
Pooled Data ◽  
Muscle Actions

A recent report suggests that differences in aerobic capacity exist between concentric and eccentric muscle action in human muscle (T. W. Ryschon, M. D. Fowler, R. E. Wysong, A. R. Anthony, and R. S. Balaban. J. Appl. Physiol. 83: 867–874, 1997). This study compared oxidative response, in the form of phosphocreatine (PCr) resynthesis rates, with matched levels of metabolic strain (i.e., changes in ADP concentration or the free energy of ATP hydrolysis) in tibialis anterior muscle exercised with either muscle action in vivo ( n = 7 subjects). Exercise was controlled and metabolic strain measured by a dynamometer and 31P-magnetic resonance spectroscopy, respectively. Metabolic strain was varied to bring cytosolic ADP concentration up to 55 μM or decrease the free energy of ATP hydrolysis to −55 kJ/mol with no change in cytoplasmic pH. PCr resynthesis rates after exercise ranged from 31.9 to 462.5 and from 21.4 to 405.4 μmol PCr/s for concentric and eccentric action, respectively. PCr resynthesis rates as a function of metabolic strain were not significantly different between muscle actions ( P > 0.40), suggesting that oxidative capacity is dependent on metabolic strain, not muscle action. Pooled data were found to more closely conform to previous biochemical measurements when a term for increasing oxidative capacity with metabolic strain was added to models of respiratory control.

scholarly journals Adenosine and ATP-sensitive potassium channels modulate dopamine release in the anoxic turtle (Trachemys scripta) striatum

2005 ◽  
Vol 289 (1) ◽  
pp. R77-R83 ◽  
Author(s):  
Sarah L. Milton ◽  
Peter L. Lutz
Keyword(s):  
Dopamine Release ◽  
Trachemys Scripta ◽  
Mammalian Brain ◽  
Freshwater Turtle ◽  
Energy Status ◽  
Gbr 12909 ◽  
Butanedione Monoxime ◽  
Intracellular Energy

Excessive dopamine (DA) is known to cause hypoxic/ischemic damage to mammalian brain. The freshwater turtle Trachemys scripta, however, maintains basal striatal DA levels in anoxia. We investigated DA balance during early anoxia when energy status in the turtle brain is compromised. The roles of ATP-sensitive potassium (KATP) channels and adenosine (AD) receptors were investigated as these factors affect DA balance in mammalian neurons. Striatal extracellular DA was determined by microdialysis with HPLC in the presence or absence of the specific DA transport blocker GBR-12909, the KATP blocker 2,3-butanedione monoxime, or the nonspecific AD receptor blocker theophylline. We found that in contrast to long-term anoxia, blocking DA reuptake did not significantly increase extracellular levels in 1-h anoxic turtles. Low DA levels in early anoxia were maintained instead by activation of KATP channels and AD receptors. Blocking KATP resulted in a 227% increase in extracellular DA in 1-h anoxic turtles but had no effect after 4 h of anoxia. Similarly, blocking AD receptors increased DA during the first hour of anoxia but did not change DA levels at 4-h anoxia. Support for the role of KATP channels in DA balance comes from normoxic animals treated with KATP opener; infusing diazoxide but not adenosine into the normoxic turtle striatum resulted in an immediate DA decrease to 14% of basal values within 1.5 h. Alternative strategies to maintain low extracellular levels may prevent catastrophic DA increases when intracellular energy is compromised while permitting the turtle to maintain a functional neuronal network during long-term anoxia.

Free energy and enthalpy of ATP hydrolysis in the sarcoplasm

1969 ◽  
Vol 174 (1036) ◽  
pp. 348-353 ◽  
Keyword(s):  
Free Energy ◽  
Ionic Strength ◽  
Temperature Dependence ◽  
Thermodynamic Data ◽  
Approximate Calculation ◽  
Atp Hydrolysis ◽  
Equilibrium Conditions ◽  
Thermodynamic Measurements

A rigorous calculation of the free energy available in vivo from ATP hydrolysis requires the following information which is not all available, namely: (i) intra­cellular pH, (ii) activities of all the species of reactants and products in sarcoplasm, (iii) thermodynamic data for all the reactions involved, including values for ionic strength and temperature dependence, and (iv) the extent of deviation from equilibrium conditions, i. e. during contraction. We shall discuss each of these factors in turn and state the assumptions made that allow the approximate calculation of the free energy made available by the following net reaction in the sarcoplasm: ATP +H 2 O → ADP + Pi + H + . (1) Although it can only be an approximation this calculation is useful since it will take into account recent thermodynamic measurements in vitro .

Studies of the biochemistry of contracting and relaxing muscle by the use of 31 P n.m.r. in conjunction with other techniques

1980 ◽  
Vol 289 (1037) ◽  
pp. 445-455 ◽  
Keyword(s):  
Free Energy ◽  
Lactic Acid ◽  
Inorganic Phosphate ◽  
Atp Hydrolysis ◽  
Free Energy Change ◽  
Energy Change ◽  
Force Development ◽  
Atp Turnover ◽  
Fundamental Information

When n.m.r. is applied to suitably chosen biological problems it yields a wealth of fundamental information unmatched by any other technique. By means of 31 P n.m.r. we have studied intact living muscle at rest, during contraction and during recovery from contraction. Phosphocreatine, ATP, inorganic phosphate, phosphorylated intermediaries of glycolysis, pH and the binding of Mg 2+ to ATP are observed directly in the spectra. From the spectra can be calculated the concentration of free ADP, the free energy change for ATP hydrolysis, the production of lactic acid and the total ATP turnover. Changes in these quantities can thus be followed continuously in vivo and we have shown how they are related to the decline in force development and to the slowing of relaxation that occur during fatigue. Similar methods have been applied to study the control of glycolysis.

Systemic Administration of Pleiotrophin Induces Hematopoietic Stem Cell Regeneration In Vivo.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1498-1498
Author(s):  
Heather A Himburg ◽  
Pamela Daher ◽  
Sarah Kristen Meadows ◽  
J. Lauren Russell ◽  
Phuong Doan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factor ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Fold Increase ◽  
Cell Regeneration ◽  
Hematopoietic Stem ◽  
Hematopoietic Reconstitution

Abstract Abstract 1498 Poster Board I-521 Significant progress has been made toward delineating the intrinsic and extrinsic signaling pathways that regulate hematopoietic stem cell (HSC) self-renewal. However, much less is known regarding the process of HSC regeneration or the extrinsic signals that regulate hematopoietic reconstitution following stress or injury. Elucidation of the microenvironmental signals which promote HSC regeneration in vivo would have important implications for the treatment of patients undergoing radiation therapy, chemotherapy and stem cell transplantation. We recently reported that pleiotrophin, a soluble heparin-binding growth factor, induced a 10-fold expansion of murine long-term repopulating HSCs in short term culture (Himburg et al. Blood (ASH Annual Meeting Abstracts), Nov 2008; 112: 78). Based on this observation, we hypothesized that PTN might also be a regenerative growth factor for HSCs. Here we tested the effect of systemic administration of PTN to non-irradiated and irradiated C57Bl6 mice to determine if PTN could promote HSC regeneration in vivo. C57Bl6 mice were irradiated with 700 cGy total body irradiation (TBI) followed by intraperitoneal administration of 2 μg PTN or saline x 7 days, followed by analysis of BM stem and progenitor cell content. Saline-treated mice demonstrated significant reductions in total BM cells, BM c-kit+sca-1+lin- (KSL) cells, colony forming cells (CFCs) and long term culture-initiating cells (LTC-ICs) compared to non-irradiated control mice. In contrast, PTN-treated mice demonstrated a 2.3-fold increase in total BM cells (p=0.03), a 5.6-fold increase in BM KSL stem/progenitor cells (p=0.04), a 2.9-fold increase in BM CFCs (p=0.004) and an 11-fold increase in LTC-ICs (p=0.03) compared to saline-treated mice. Moreover, competitive repopulating transplantation assays demonstrated that BM from PTN-treated, irradiated mice contained 5-fold increased competitive repopulating units (CRUs) compared to saline-treated, irradiated mice (p=0.04). Taken together, these data demonstrate that the administration of PTN induces BM HSC and progenitor cell regeneration in vivo following injury. Comparable increases in total BM cells, BM KSL cells and BM CFCs were also observed in PTN-treated mice compared to saline-treated controls following 300 cGy TBI, demonstrating that PTN is a potent growth factor for hematopoietic stem/progenitor cells in vivo at less than ablative doses of TBI. In order to determine whether PTN acted directly on BM HSCs to induce their proliferation and expansion in vivo, we exposed mice to BrDU in their drinking water x 7 days and compared the response to saline treatment versus PTN treatment. PTN-treated mice demonstrated a significant increase in BrDU+ BM KSL cells compared to saline-treated controls (p=0.04) and cell cycle analysis confirmed a significant increase in BM KSL cells in S phase in the PTN-treatment group compared to saline-treated controls (p=0.04). These data indicate that PTN serves as a soluble growth factor for BM HSCs and induces their proliferation and expansion in vivo while preserving their repopulating capacity. These results suggest that PTN has therapeutic potential as a novel growth factor to accelerate hematopoietic reconstitution in patients undergoing myelosuppressive radiotherapy or chemotherapy. Disclosures: No relevant conflicts of interest to declare.

Alemtuzumab Treatment Can Affect CD52 Positive As Well As CD52 Negative GPI-Deficient, Sezary Cells Allowing Long-Term Disease Control

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2491-2491
Author(s):  
C.J.M. Halkes ◽  
I Jedema ◽  
H.M. van Egmond ◽  
L van der Fits ◽  
J.H.F. Falkenburg ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Fold Increase ◽  
Cell Populations ◽  
Proliferative Potential ◽  
Small Populations ◽  
Collateral Damage ◽  
Sézary Cells

Abstract Abstract 2491 Alemtuzumab (ALT) is a monoclonal anti CD52 antibody used for the treatment of CD52 positive lymphoid malignancies and to deplete T cells in vivo and in vitro to prevent graft rejection or GVHD after allogeneic stem cell transplantation (alloSCT). Membrane CD52 expression depends on the presence of a glycosylphosphatidylinositol (GPI) anchor. GPI deficiency is frequently found in small populations of normal and malignant hematopoietic cells, including T and B cells (frequencies from <0.01 to 2%). These cells lack expression of GPI-linked proteins like CD52 as can be detected by absence of staining of FLAER, which is an aerolysin that specifically binds to mammalian GPI anchors. After alloSCT using ALT for T cell depletion, reconstitution of FLAER and CD52 double negative cells is seen, and outgrowth of CD52 negative malignant cell populations has been found after single agent treatment with ALT in malignant diseases. However, GPI deficient cells have been suggested to have a lower proliferative potential and a decreased survival due to their increased susceptibility to spontaneous complement mediated cell lysis, possibly explaining the infrequent dominant outgrowth of GPI deficient clones in healthy individuals. Sézary Syndrome (SS) is an aggressive cutaneous T cell lymphoma characterized by the presence of high numbers of neoplastic T cells expressing CD4 and CD52 in peripheral blood, lymph nodes and skin. Clinical responses in SS patients after single drug treatment with low dosed ALT have been described by several investigators. However, in 6 out of 6 patients analyzed, we found a small population of CD52 and FLAER negative Sézary cells, illustrating that a GPI negative subpopulation is frequently observed which may lead to outgrowth of CD52 negative Sézary cells. We treated 3 patients with successive courses of low dose ALT (10 mg subcutaneously once weekly until circulating malignant cells were < 1,000/mm3) and followed the kinetics of CD52- and CD52+ Sézary cells. Before ALT treatment, a CD4+CD52-FLAER- T cell population was found in all three patients (0.01–0.06% of all circulating CD4+ T cells). As expected, a rapid decrease in absolute numbers of CD4+CD52+FLAER+ cells was observed after ALT treatment (decrease 94 to 100%). Surprisingly, despite the absence of the CD52 target molecule, the absolute number of CD4+CD52-FLAER- T cells also decreased after the first and second treatment cycles in all three patients (decreases between 22 and 96%), indicating that the massive in vivo ALT mediated lysis of CD52+ Sézary cells coincided with collateral damage of CD52- Sézary cells. Between successive treatment courses in the absence of circulating ALT, the absolute numbers of CD4+CD52+FLAER+ T cells showed a more rapid increase compared to CD4+CD52-FLAER- T cells in all patients (median 193 fold increase (range 17–896) versus 9 fold increase (range 2–144) respectively), illustrating a decreased in vivo proliferative potential of these GPI negative cells. After repeated doses of ALT, one of the patients developed resistance to ALT treatment. Phenotype analysis revealed that 97% of the 23,000/mm3 circulating Sézary cells were CD4+CD52-FLAER-. Clonality analysis showed that CD4+CD52+FLAER+ and CD4+CD52-FLAER–Sézary cell populations expressed identical T cell receptor V-beta chains demonstrating that both cell populations are part of the same initial clone of Sézary cells. At present, one year after the start of ALT treatment, reponses are still observed in both other patients without overgrowth of a CD4+CD52-FLAER–Sézary cells. We conclude that despite presence of small populations of CD52 and GPI negative cells in patients with Sézary Syndrome, all patients respond to treatment with alemtuzumab. CD52 negative, GPI deficient Sézary cells showed high susceptibility to collateral damage during antibody treatment. During treatment intervals, CD52+ cells showed a faster recovery compared to CD52- cells, indicating a lower proliferative potential of the GPI deficient Sézary cells. Although, as shown in one patient, ultimate outgrowth of GPI deficient CD52- sezary cells can occur, the capacity to achieve long term control of both CD52+ and CD52- Sézary cells in several patients offers a rationale for treatment of SS with alemtuzumab, possibly in combination with a low dosed cytotoxic drug Disclosures: Off Label Use: Alemtuzumab for treatment of Sezary Syndrome.

scholarly journals Low Brain Intracellular Free Magnesium in Mitochondrial Cytopathies

1999 ◽  
Vol 19 (5) ◽  
pp. 528-532 ◽  
Author(s):  
Bruno Barbiroli ◽  
Stefano Iotti ◽  
Pietro Cortelli ◽  
Paolo Martinelli ◽  
Raffaele Lodi ◽  
...  
Keyword(s):  
Free Energy ◽  
Respiratory Chain ◽  
Atp Hydrolysis ◽  
Coenzyme Q ◽  
Functional Relation ◽  
Brain Cell ◽  
Resonance Spectroscopy ◽  
Mitochondrial Cytopathies ◽  
Free Magnesium

The authors studied, by in vivo phosphorus magnetic resonance spectroscopy (31P-MRS), the occipital lobes of 19 patients with mitochondrial cytopathies to clarify the functional relation between energy metabolism and concentration of cytosolic free magnesium. All patients displayed defective mitochondrial respiration with low phosphocreatine concentration [PCr] and high inorganic phosphate concentration [Pi] and [ADP]. Cytosolic free [Mg2+] and the readily available free energy (defined as the actual free energy released by the exoergonic reaction of ATP hydrolysis, i.e., ΔGATPhyd) were abnormally low in all patients. Nine patients were treated with coenzyme Q10 (CoQ), which improved the efficiency of the respiratory chain, as shown by an increased [PCr], decreased [Pi] and [ADP], and increased availability of free energy (more negative value of ΔGATPhyd). Treatment with CoQ also increased cytosolic free [Mg2+] in all treated patients. The authors findings demonstrate low brain free [Mg2+] in our patients and indicate that it resulted from failure of the respiratory chain. Free Mg2+ contributes to the absolute value of ΔGATPhyd. The results also are consistent with the view that cytosolic [Mg2+] is regulated in the intact brain cell to equilibrate, at least in part, any changes in rapidly available free energy.

Sign in / Sign up

Export Citation Format

Share Document