The relative time course of early changes in mitochondrial function and intracellular pH during hypoxia in the isolated toad ventricle strip.

The purpose of this study was to evaluate the usefulness of in vivo 31P magnetic resonance spectroscopy (MRS) for monitoring changes in growth-related phosphate metabolite concentration and intracellular pH value in rabbit thigh muscle implanted with VX-2 carcinoma. The time-course magnetic resonance imaging (MRI) and in vivo 31P MRS were examined weekly in the course of 10 weeks following the onset of a VX-2 carcinoma implantation. The spectra were quantitatively analyzed to obtain vital information on the time course variation of the phosphorus metabolites and intracellular pH value according to the tumor growth. Elevation in the concentrations of phosphormonoesters (PME), inorganic phosphate (Pi), and phosphodiesters (PDE) was observed over the time course of 3-4 weeks after the implantation of VX2 carcinoma, while the rest of the metabolites, PCr and ATP tended to be constant. The concentration changes of PME, Pi, and PDE were positively correlated with the volumes of tumor necrosis. The intracellular pH values decreased with the time course of tumor growth and the volumes of tumor necrosis. In vivo 31P MRS is capable of non-invasive monitoring of intracellular pH values as well as the concentration changes of phosphate metabolites during tumor growth.

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Spreading of human endothelial cells on fibronectin or vitronectin triggers elevation of intracellular free calcium.

The Journal of Cell Biology ◽

10.1083/jcb.120.4.1003 ◽

1993 ◽

Vol 120 (4) ◽

pp. 1003-1010 ◽

Cited By ~ 164

Author(s):

M A Schwartz

Keyword(s):

Endothelial Cells ◽

Calcium Channels ◽

Intracellular Ph ◽

Time Course ◽

Single Cells ◽

State Level ◽

Cell Spreading ◽

Free Calcium ◽

Voltage Dependent ◽

Voltage Dependent Calcium Channels

Intracellular calcium ([Ca2+]i) was measured in FURA 2-loaded endothelial cells plated on fibronectin or vitronectin. Average values for [Ca2+]i increased to approximately twofold above basal levels by approximately 1 h after plating, and then declined. The increase in [Ca2+]i required extracellular calcium. Substituting potassium for sodium in the medium reduced the elevation of [Ca2+]i, a result that rules out the involvement of Na-Ca exchangers or voltage-dependent calcium channels, but that is consistent with the involvement of voltage-independent calcium channels. Plating cells on an anti-integrin beta 1 subunit antibody gave a similar [Ca2+]i response, but clustering beta 1 integrins with the same antibody, or occupying integrins with RGD (arg-gly-asp) peptides had no effect. Time course measurements on single cells revealed that in each cell [Ca2+]i rose abruptly at some point during spreading, from the basal level to a higher steady-state level that was maintained for some time. The elevated [Ca2+]i was unrelated to previously observed changes in intracellular pH, because chelating the Ca2+ in the medium failed to inhibit the elevation of pHi that occurred during cell spreading. In conclusion, these results show that integrin-mediated cell spreading can regulate [Ca2+]i, and the pathways involved are distinct from those that regulate intracellular pH.

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A Highly Temperature-sensitive Proton Current in Mouse Bone Marrow–derived Mast Cells

The Journal of General Physiology ◽

10.1085/jgp.109.6.731 ◽

1997 ◽

Vol 109 (6) ◽

pp. 731-740 ◽

Cited By ~ 36

Author(s):

Miyuki Kuno ◽

Junko Kawawaki ◽

Fusao Nakamura

Keyword(s):

Bone Marrow ◽

Mast Cells ◽

Intracellular Ph ◽

Time Course ◽

Reversal Potential ◽

Outward Current ◽

Temperature Sensitive ◽

Mouse Bone Marrow ◽

Bafilomycin A1 ◽

Ph Homeostasis

Proton (H+) conductive pathways are suggested to play roles in the regulation of intracellular pH. We characterized temperature-sensitive whole cell currents in mouse bone marrow–derived mast cells (BMMC), immature proliferating mast cells generated by in vitro culture. Heating from 24 to 36°C reversibly and repeatedly activated a voltage-dependent outward conductance with Q10 of 9.9 ± 3.1 (mean ± SD) (n = 6). Either a decrease in intracellular pH or an increase in extracellular pH enhanced the amplitude and shifted the activation voltage to more negative potentials. With acidic intracellular solutions (pH 5.5), the outward current was detected in some cells at 24°C and Q10 was 6.0 ± 2.6 (n = 9). The reversal potential was unaffected by changes in concentrations of major ionic constituents (K+, Cl−, and Na+), but depended on the pH gradient, suggesting that H+ (equivalents) is a major ion species carrying the current. The H+ current was featured by slow activation kinetics upon membrane depolarization, and the activation time course was accelerated by increases in depolarization, elevating temperature and extracellular alkalization. The current was recorded even when ATP was removed from the intracellular solution, but the mean amplitude was smaller than that in the presence of ATP. The H+ current was reversibly inhibited by Zn2+ but not by bafilomycin A1, an inhibitor for a vacuolar type H+-ATPase. Macroscopic measurements of pH using a fluorescent dye (BCECF) revealed that a rapid recovery of intracellular pH from acid-load was attenuated by lowering temperature, addition of Zn2+, and depletion of extracellular K+, but not by bafilomycin A1. These results suggest that the H+ conductive pathway contributes to intracellular pH homeostasis of BMMC and that the high activation energy may be involved in enhancement of the H+ conductance.

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Time course of red blood cell intracellular pH recovery following short-circuiting in relation to venous transit times in rainbow trout, Oncorhynchus mykiss

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00062.2018 ◽

2018 ◽

Vol 315 (2) ◽

pp. R397-R407 ◽

Cited By ~ 7

Author(s):

Till S. Harter ◽

Alexandra G. May ◽

William J. Federspiel ◽

Claudiu T. Supuran ◽

Colin J. Brauner

Keyword(s):

Rainbow Trout ◽

Blood Cell ◽

Intracellular Ph ◽

Red Blood Cell ◽

Time Course ◽

Ph Sensitive ◽

Adrenergic Stimulation ◽

Rainbow Trout Oncorhynchus Mykiss ◽

Athletic Ability

Accumulating evidence is highlighting the importance of a system of enhanced hemoglobin-oxygen (Hb-O2) unloading for cardiovascular O2 transport in teleosts. Adrenergically stimulated sodium-proton exchangers (β-NHE) create H+ gradients across the red blood cell (RBC) membrane that are short-circuited in the presence of plasma-accessible carbonic anhydrase (paCA) at the tissues; the result is a large arterial-venous pH shift that greatly enhances O2 unloading from pH-sensitive Hb. However, RBC intracellular pH (pHi) must recover during venous transit (31–90 s) to enable O2 loading at the gills. The halftimes ( t1/2) and magnitudes of RBC β-adrenergic stimulation, short-circuiting with paCA and recovery of RBC pHi, were assessed in vitro, on rainbow trout whole blood, and using changes in closed-system partial pressure of O2 as a sensitive indicator for changes in RBC pHi. In addition, the recovery rate of RBC pHi was assessed in a continuous-flow apparatus that more closely mimics RBC transit through the circulation. Results indicate that: 1) the t1/2 of β-NHE short-circuiting is likely within the residence time of blood in the capillaries, 2) the t1/2 of RBC pHi recovery is 17 s and within the time of RBC venous transit, and 3) after short-circuiting, RBCs reestablish the initial H+ gradient across the membrane and can potentially undergo repeated cycles of short-circuiting and recovery. Thus, teleosts have evolved a system that greatly enhances O2 unloading from pH-sensitive Hb at the tissues, while protecting O2 loading at the gills; the resulting increase in O2 transport per unit of blood flow may enable the tremendous athletic ability of salmonids.

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Time course of liver mitochondrial function and intrinsic changes in oxidative phosphorylation in a rat model of sepsis

Intensive Care Medicine Experimental ◽

10.1186/s40635-018-0197-y ◽

2018 ◽

Vol 6 (1) ◽

Cited By ~ 10

Author(s):

Pierre Eyenga ◽

Damien Roussel ◽

Jerome Morel ◽

Benjamin Rey ◽

Caroline Romestaing ◽

...

Keyword(s):

Oxidative Phosphorylation ◽

Rat Model ◽

Mitochondrial Function ◽

Time Course

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Parallel Processing of Semantics and Phonology in Spoken Production: Evidence from Blocked Cyclic Picture Naming and EEG

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_01675 ◽

2021 ◽

pp. 1-14 ◽

Cited By ~ 1

Author(s):

Chen Feng ◽

Markus F. Damian ◽

Qingqing Qu

Keyword(s):

Cognitive Processes ◽

Language Production ◽

Semantic Processing ◽

Time Course ◽

Time Window ◽

Early Stage ◽

Phonological Information ◽

Relative Time ◽

Similar Time ◽

Semantic Access

Spoken language production involves lexical-semantic access and phonological encoding. A theoretically important question concerns the relative time course of these two cognitive processes. The predominant view has been that semantic and phonological codes are accessed in successive stages. However, recent evidence seems difficult to reconcile with a sequential view but rather suggests that both types of codes are accessed in parallel. Here, we used ERPs combined with the “blocked cyclic naming paradigm” in which items overlapped either semantically or phonologically. Behaviorally, both semantic and phonological overlap caused interference relative to unrelated baseline conditions. Crucially, ERP data demonstrated that the semantic and phonological effects emerged at a similar latency (∼180 msec after picture onset) and within a similar time window (180–380 msec). These findings suggest that access to phonological information takes place at a relatively early stage during spoken planning, largely in parallel with semantic processing.

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Nonlinear stiffness–force relationships in whole mammalian skeletal muscles

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y86-209 ◽

1986 ◽

Vol 64 (9) ◽

pp. 1236-1244 ◽

Cited By ~ 29

Author(s):

R. B. Stein ◽

T. Gordon

Keyword(s):

Skeletal Muscles ◽

Time Course ◽

Isometric Contractions ◽

Nonlinear Stiffness ◽

Relative Time ◽

Nonlinear Relation ◽

Length Changes ◽

Slow Twitch ◽

Elastic Elements ◽

Series Elastic

Small, sinusoidal length changes were superimposed on isometric contractions of fast- and slow-twitch mouse muscles, which were stimulated maximally via their nerves. Stiffness increased with increasing frequency of sinusoidal stimulation, but the relative time course of force and stiffness changes during twitch, tetanic, or partially fused contractions was quite invariant over a range of frequencies in both muscles. Typically, stiffness increases more rapidly than force during contraction and decreases less rapidly during relaxation. This pattern was observed at various temperatures and with various numbers of stimuli. It can be described by a nonlinear relation between stiffness and force with some hysteresis. The presence in the muscle of parallel and series elastic elements, whose stiffness varies with force, may account for the nonlinear relation. This nonlinearity can be used to relate the patterns for summation of force and stiffness observed with brief trains of stimuli under a variety of conditions.

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Cardiac phase-dependent time normalization reduces load dependence of time-varying elastance

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00785.2008 ◽

2009 ◽

Vol 296 (2) ◽

pp. H342-H349 ◽

Cited By ~ 3

Author(s):

Taco Kind ◽

Nico Westerhof ◽

Theo J. C. Faes ◽

Jan-Willem Lankhaar ◽

Paul Steendijk ◽

...

Keyword(s):

Time Course ◽

Cardiac Cycle ◽

Time Varying ◽

Mean Square ◽

Cardiac Phase ◽

Relative Time ◽

Comprehensive Description ◽

Load Dependence ◽

Volume Measurements ◽

Isovolumic Relaxation

The time-varying elastance concept provides a comprehensive description of the intrinsic mechanical properties of the left ventricle that are assumed to be load independent. Based on pressure-volume measurements obtained with combined pressure conductance catheterization in six open-chest anesthetized sheep, we show that the time to reach end systole (defined as maximal elastance) is progressively prolonged for increasing ventricle pressures, which challenges the original (load-independent) time-varying elastance concept. Therefore, we developed a method that takes into account load dependency by normalization of time course of the four cardiac phases (isovolumic contraction, ejection, isovolumic relaxation, filling) individually. With this normalization, isophase lines are obtained that connect points in pressure-volume loops of different beats at the same relative time in each of the four cardiac phases, instead of isochrones that share points at the same time in a cardiac cycle. The results demonstrate that pressure curves can be predicted with higher accuracy, if elastance curves are estimated using isophase lines instead of using isochrones [root-mean-square error (RMSE): 3.8 ± 1.0 vs. 14.0 ± 7.4 mmHg ( P < 0.001), and variance accounted for (VAF): 94.8 ± 1.3 vs. 78.6 ± 14.8% ( P < 0.001)]. Similar results were found when the intercept volume was assumed to be time varying [RMSE: 1.7 ± 0.3 vs. 13.4 ± 7.4 mmHg ( P < 0.001), and VAF: 97.4 ± 0.5 vs. 81.8 ± 15.5% ( P < 0.001)]. In conclusion, phase-dependent time normalization reduces cardiac load dependency of timing and increases accuracy in estimating time-varying elastance.

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Time course of blood lactate levels, inflammation, and mitochondrial function in experimental sepsis

Critical Care ◽

10.1186/s13054-017-1691-4 ◽

2017 ◽

Vol 21 (1) ◽

Cited By ~ 11

Author(s):

Thiago Domingos Corrêa ◽

Adriano José Pereira ◽

Sebastian Brandt ◽

Madhusudanarao Vuda ◽

Siamak Djafarzadeh ◽

...

Keyword(s):

Blood Lactate ◽

Mitochondrial Function ◽

Time Course ◽

Experimental Sepsis ◽

Lactate Levels ◽

Blood Lactate Levels

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Mitochondrial-specific autophagy linked to mitochondrial dysfunction following traumatic freeze injury in mice

AJP Cell Physiology ◽

10.1152/ajpcell.00123.2019 ◽

2020 ◽

Vol 318 (2) ◽

pp. C242-C252 ◽

Cited By ~ 2

Author(s):

Anna S. Nichenko ◽

W. Michael Southern ◽

Kayvan Forouhesh Tehrani ◽

Anita E. Qualls ◽

Alexandra B. Flemington ◽

...

Keyword(s):

Skeletal Muscle ◽

Mitochondrial Dysfunction ◽

Protein Content ◽

Mitochondrial Function ◽

Time Course ◽

Related Protein ◽

Autophagy Flux ◽

Adult Skeletal Muscle ◽

Freeze Injury ◽

Autophagy Induction

The objective of this study was to interrogate the link between mitochondrial dysfunction and mitochondrial-specific autophagy in skeletal muscle. C57BL/6J mice were used to establish a time course of mitochondrial function and autophagy induction after fatigue ( n = 12), eccentric contraction-induced injury ( n = 20), or traumatic freeze injury (FI, n = 28); only FI resulted in a combination of mitochondrial dysfunction, i.e., decreased mitochondrial respiration, and autophagy induction. Moving forward, we tested the hypothesis that mitochondrial-specific autophagy is important for the timely recovery of mitochondrial function after FI. Following FI, there is a significant increase in several mitochondrial-specific autophagy-related protein contents including dynamin-related protein 1 (Drp1), BCL1 interacting protein (BNIP3), Pink1, and Parkin (~2-fold, P < 0.02). Also, mitochondrial-enriched fractions from FI muscles showed microtubule-associated protein light chain B1 (LC3)II colocalization suggesting autophagosome assembly around the damaged mitochondrial. Unc-51 like autophagy activating kinase (Ulk1) is considered necessary for mitochondrial-specific autophagy and herein we utilized a mouse model with Ulk1 deficiency in adult skeletal muscle ( myogenin-Cre). While Ulk1 knockouts had contractile weakness compared with littermate controls (−27%, P < 0.02), the recovery of mitochondrial function was not different, and this may be due in part to a partial rescue of Ulk1 protein content within the regenerating muscle tissue of knockouts from differentiated satellite cells in which Ulk1 was not genetically altered via myogenin-Cre. Lastly, autophagy flux was significantly less in injured versus uninjured muscles (−26%, P < 0.02) despite the increase in autophagy-related protein content. This suggests autophagy flux is not upregulated to match increases in autophagy machinery after injury and represents a potential bottleneck in the clearance of damaged mitochondria by autophagy.

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