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Biomedical subjects

C Juel

Publications and source records attributed to C Juel.

At least 37 records · Page 2Linked to original sources
PubMed1998

Lactate/H+ transport in skeletal muscle from spinal-cord-injured patients.

In order to evaluate the effect of prolonged muscle inactivity on sarcolemmal lactate/H+ transport in humans, the lactate/H+ transport capacity was determined in the thigh muscle of spinal-cord-injured (SCI) individuals. The lactate transport rate was measured in sarcolemmal giant vesicles produced by collagenase treatment of muscle biopsies obtained from the vastus lateralis muscle. Six SCI subjects with total loss of motor and sensory functions of their lower limbs participated in the study. The duration of the injury ranged from 2 to 15 years. The total lactate transport rate in the muscle of SCI patients was 46.5 +/- 2.6 pmol.cm-2.s-1 (mean +/- SEM), which corresponds to a 17% lower (P < 0.05) transport rate than that found in healthy, untrained subjects. The estimated carrier-mediated lactate/H+ transport capacity was approximately 26% lower in the SCI patients than in healthy, untrained subjects. The observed muscle lactate/H+ transport capacity of SCI individuals is in accordance with a positive correlation between the capacity of the lactate/H+ transporters and the percentage occurrence of slow-twitch fibres in a muscle, although there seems to be a wide range of transport capacities within each fibre type. The present results show that the sarcolemmal lactate/H+ transport capacity is lower in SCI individuals than in normally physically active subjects, which indicates that prolonged muscle inactivity reduces the lactate/H+ transport capacity of human muscle.

Adult↗
PubMed1997

Dissociation between lactate and proton exchange in muscle during intense exercise in man.

1. Transport of lactate, H+ and fluid across muscle sarcolemma was studied in contracting muscles under varying blood acid-base conditions. 2. Subjects performed two-legged submaximal knee-extensor exercise for 29-35 min consisting of warming up for 5 min followed by 10 min of leg exercise (L1), leg and arm exercise for 6-10 min (L2 + A) and leg exercise for 10 min (L3). The experimental protocol was performed on two occasions; inspiring air (normoxia, N) or breathing 14% O2 in N2 (hypoxia, H). Leg blood flow was measured and femoral arterial and venous blood was sampled before and during each phase of exercise. 3. Arterial blood lactate concentration increased progressively during exercise to 5.9 +/- 0.8 (N) and 8.2 +/- 0.8 mmol l-1 (H) (P < 0.05) after 5.5 min of L2 + A. Arterial blood pH was higher (P < 0.05) in H than in N, whereas arterial blood HCO3- concentrations were the same. Leg lactate release was higher in H than in N (3.1 +/- 0.7 vs. 2.0 mmol l-1 (P < 0.05) during L1. In L2 + A a net uptake of lactate was observed in both N and H. The concentration of lactate in the red blood cells increased during exercise to 2.3 +/- 0.4 (N) and 4.3 +/- 0.7 mmol l-1 (H) (P < 0.05) after 5.5 min of L2 + A, but no red blood cell femoral arterial-venous lactate difference was observed. 4. Net proton release, estimated from actual base excess (ABE) adjusted for changes in reduced haemoglobin, was significant (P < 0.05) both at rest and during each phase of exercise. Furthermore, the difference between net proton and lactate release was positive throughout exercise and of similar magnitude in N and H. 5. The present data suggest that (1) H+ exchange in muscle during submaximal exercise can to a large extent occur through mechanisms other than via coupling to lactate; (2) muscle transport of H+ is insensitive to changes in blood pH in the range of 0.02-0.08 pH units; (3) transport of lactate across the membrane of red blood cells appears to be of minor importance for lactate release from active muscles.

Acid-Base Equilibrium↗
PubMed1997

Lactate-proton cotransport in skeletal muscle.

Skeletal muscle and most other tissues possess a membrane transport system mediating a coupled lactate and H+ translocation. Muscle possesses several lactate-proton transporter isoforms of which two have been cloned; however, the main isoform remains to be identified. The isoforms may have different properties and functional roles, but these have not been specifically characterized. The distribution of lactate-proton transport capacity in skeletal muscle is fiber type dependent, with a higher capacity in slow-twitch fibers compared with fast-twitch fibers. During intense muscle activity and in the recovery period, the lactate and H+ effluxes are mainly mediated by the lactate-proton transporter, which reduces the accumulation of lactate in muscle as well as the drop in internal pH suggested to be involved in muscle fatigue. Thus the lactate-proton transporter is of functional importance for pH regulation in association with muscle activity. This carrier is also important for lactate uptake into resting muscle and other tissues; therefore, the carrier distribution is important for the fate of lactate in the body. In addition, the capacity of the lactate-proton transporter can be increased by intense training and is reduced by inactivity; thus the lactate-proton transporter can undergo adaptive changes.

Animals↗
PubMed1996

Symmetry and pH dependency of the lactate/proton carrier in skeletal muscle studied with rat sarcolemmal giant vesicles.

Muscle lactate transport was studied in rat sarcolemmal giant vesicles, in which the membrane orientation was similar to that of intact cells. The lactate concentration dependency was studied using influx experiments under equilibrium exchange. zero-trans. and infinite-cis conditions. At constant external and internal pH the carrier behaved symmetrically with regard to lactate transport from the two sides of the membrane. Lactate at the trans side stimulated the lactate tracer flux (trans-acceleration). Both in zero-trans influx and efflux experiments the lactate flux was stimulated in a symmetric way by H+ at the cis side, consistent with protons being the substrate for the carrier. In contrast, the lactate flux was symmetrically inhibited by H+ at the trans side (trans-inhibition), the underlying mechanism is likely that the protonated carrier with no lactate bound is unable to reorient in the membrane. These findings have implications both for the kinetic model and for understanding the physiological function of the lactate/proton transporter.

Animals↗
PubMed1996

Chronic muscle stimulation increases lactate transport in rat skeletal muscle.

The aim of this study was to examine the effects of chronic low frequency stimulation on the lactate transport across the plasma membrane of the tibialis anterior (TA) muscle of the rat. Stimulating electrodes were implanted on either side of the peroneal nerve in one hindlimb. Chronic stimulation (10 Hz, 50 microsecond bursts, 24h/day) commenced 7 days after surgery, and were continued for 7 days. Animals were then left for 24 h, and thereafter muscles were obtained. Cytochrome C-oxidase activity was increased 1.9-fold in the stimulated TA compared to the control TA (p < 0.05). Lactate transport (zero-trans) was measured in giant sarcolemmal vesicles obtained from the chronically stimulated TA and the control TA. At each of the concentrations used in these studies a significant increase in lactate transport was observed; 2.8-fold increase at 1 mM lactate p < 0.05); 2-fold increases at both 30 mM and 50 mM lactate p < 0.05). These studies have shown that lactate transport capacity is markedly increased in response to chronic muscle contraction.

Action Potentials↗
PubMed1996

Lactate/proton co-transport in skeletal muscle: regulation and importance for pH homeostasis.

In skeletal muscle, intracellular pH is more alkaline than would be predicted if H+ were passively distributed across the sarcolemma. Therefore, the passive influx of H+ must be counteracted by transport processes mediating H+ afflux. In resting skeletal muscle, these transport processes are Na+/H+ exchange and bicarbonate-dependent systems. During periods of high energy demand, skeletal muscle produces large amounts of lactic acid. The internal accumulation of lactic acid reduces pH, which may cause fatigue. It is therefore important for muscle cells to be able to regulate pH during and after activity. A part of the accumulated lactate and H+ is metabolized, but a considerable fraction is released from the cell. The efflux of H+ and lactate might be mediated by the lactate/proton co-transport system found in almost all cell types in the body. The role of lactate/proton co-transport in pH regulation has been studied both with intact cells and with sarcolemmal vesicles. In intact cells, inhibitors of lactate/proton transport have been shown to accelerate the development of fatigue, and to delay the recovery after activity. A comparison with vesicles has demonstrated that, at low pH, and with a high lactate concentration, the capacity for H+ removal is higher via the lactate/proton co-transport system than via the sum of the Na+/H+ exchange and bicarbonate-dependent exchange systems. Therefore, the carrier-mediated lactate/proton efflux is of major importance for pH regulation in connection with muscle activity. The lactate/proton transport system has been shown to undergo long-term changes depending on the level of physical activity. The capacity of the system was enhanced after intense training or chronic stimulation, and reduced after denervation. It is concluded that the lactate/proton transport system is of major importance for pH regulation in skeletal muscle, and that changes in the amount of transporters are one of the many adaptations to physical activity.

Animals↗
PubMed1995

Regulation of cellular pH in skeletal muscle fiber types, studied with sarcolemmal giant vesicles obtained from rat muscles.

Sarcolemmal giant vesicles obtained from rat hindlimb muscles were used as a model for the study of pH regulation in skeletal muscle. The transport systems involved in the recovery from 40 mM lactate and pHi 6.5 were quantified from both flux measurements of the co-transported ions and counter-ions, and from measurements of the rate of the internal pH change. The diffusion of lactic acid plus the carrier-mediated co-transport of lactate and H+ had the highest capacity to transport protons (240 nmol H+/mg protein per min). These systems are therefore responsible for a large part of the H+ efflux in periods with a high lactate production. The capacity of the HCO(3)- - dependent systems was 47 nmol/mg per min, and the capacity of the Na+/H+ exchange system was 33 nmol/mg per min in vesicles from mixed muscles. The capacity to remove H+ by the lactate/H+ co-transport system and by the bicarbonate-dependent systems was significantly higher in vesicles from predominantly red fibers than in vesicles from white fibers, whereas the distribution of the Na+/H+ exchange system was independent of fiber type. These observations demonstrate that the pH regulation during muscle activity in red muscles is more effective than in white muscles.

Animals↗
PubMed1995

Lactate transport studied in sarcolemmal giant vesicles from rat skeletal muscles: effect of denervation.

The effect of denervation on lactate transport capacity was studied in giant sarcolemmal vesicles obtained from rat muscle. The rate of lactate transport was determined in soleus and red (RG) and white gastrocnemius (WG) after 1, 3, and 21 days of denervation and in the corresponding contralateral muscles. In addition, muscle lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) activities were determined. After 1, 3, and 21 days of denervation the rate of lactate transport was lower (P < 0.05) in WG (9, 11, and 36%), RG (15, 21, and 41%), and soleus (12, 24, and 50%) compared with the contralateral muscles. After 21 days of denervation LDH activity was 26, 25, and 34% and SDH activity 33, 25, and 27% lower (P < 0.05) in WG, RG, and soleus, respectively, compared with the contralateral muscles. In the control muscles the lactate transport capacity was 20 and 32% lower (P < 0.05) in WG than in RG and soleus, respectively. The present findings provide support that the sarcolemmal lactate carrier is a plastic system; the transport capacity in soleus, RG, and WG already declines after 1 day of denervation and is further reduced after 21 days of denervation. In addition, the data suggest that the lactate transport capacity in fast-twitch glycolytic fibers < fast-twitch oxidative-glycolytic fibers < slow-twitch oxidative fibers.

Animals↗
PubMed1995

Effect of blood flow on muscle lactate release studied in perfused rat hindlimb.

The influence of blood flow on muscle lactate and H+ release as well as muscle glyconeogenesis was studied in the perfused rat hindlimb. After 2 min of supramaximal stimulation the perfusate flow rate was 7 (F7), 12 (F12), or 18 (F18) ml/min for 30 min. Perfusate samples were drawn frequently and muscle samples were obtained before stimulation, immediately after stimulation, and at 3, 10, and 30 min of recovery from soleus, white gastrocnemius (WG) and red gastrocnemius. During the first 5 min of recovery lactate release was 35-39% lower (P < 0.05) in F7 than in F12 and F18 but with no differences in total release during recovery. In F7 the concentration of lactate was higher (P < 0.05) in soleus after 10 min (18-20%) and in WG after 30 min (63-67%) than in F12 and F18. During the first 2 min of recovery H+ release was 23-34% lower (P < 0.05) in F7 than in F12 and F18. The difference between H+ and lactate release was larger (P < 0.05) in F7 than in F12 and F18 from 3 to 10 min and from 5 to 10 min of recovery, respectively. Muscle glycogen concentrations after 30 min of recovery were independent of flow in each of the muscles. The present data suggest that 1) in the range of blood flow rates from 0.61 to 0.92 ml.min-1.g-1, lactate and H+ release are independent of the flow rate, whereas at a lower flow rate (0.36 ml.min-1.g-1) release of these substances is decreased; 2) low blood flow influences lactate efflux more than H+ release; and 3) muscle glyconeogenesis from lactate is of minor importance.

Acid-Base Equilibrium↗
PubMed1994

Reconstitution of the lactate carrier from rat skeletal-muscle sarcolemma.

The lactate carrier was solubilized from purified rat skeletal-muscle sarcolemma with the detergent decanoyl-N-methyl-glucamide and the solubilized carrier was reconstituted into phospholipid vesicles. Reconstituted proteoliposomes showed a faster time course of L-lactate uptake than did protein-free liposomes. The rate of L-lactate uptake into the proteoliposomes was inhibited by the lactate-transport inhibitors p-chloromercuribenzenesulphonate, diethyl pyrocarbonate, alpha-cyano-4-hydroxycinnamate and quercetin. In contrast, the anion-exchange inhibitor DIDS (4,4'-di-isothiocyanostilbene-2,2'-disulphonate) had almost no effect on the uptake. The extent of L-lactate uptake at equilibrium was not affected by the presence of the transport inhibitors, but was sensitive to osmotic strength. L-Lactate and pyruvate, but not D-lactate, inhibited L-lactate uptake when present at 10-fold excess. The properties of L-lactate transport in reconstituted proteoliposomes were similar to those observed in native sarcolemmal vesicles, i.e. the lactate carrier seems to retain its transport characteristics during the solubilization and reconstitution steps.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Effect of glucose-6-phosphate and pH on glucose transport in skeletal muscle plasma membrane giant vesicles.

The effect of glucose-6-phosphate (G-6-P) and pH on glucose transport was studied in skeletal muscle plasma membrane giant vesicles containing GLUT4 but not GLUT1. Vesicles (average diameter 7.6 microns) were obtained by collagenase treatment of muscle. The vesicles were incubated with 10 mmol l-1 G-6-P and, after 0.5 and 2 h of incubation, the intravesicular G-6-P concentration was 0.93 +/- 0.4 mmol l-1 and 1.18 +/- 0.5 mmol l-1 (mean +/- SE, n = 4), respectively. In order to increase the intravesicular G-6-P concentration, 0.001% saponin was added during incubation, which increased the 2-h intravesicular G-6-P concentration to 4.57 +/- 1.0 mmol l-1 (n = 4). Initially, vesicles were used for glucose transport studies after 30 min of incubation with 10 mmol l-1 of G-6-P. There was no effect of G-6-P on either the affinity constant (Km) or maximal velocity (Vmax) of the glucose transport. Subsequently, vesicles were incubated for 2 h with 10 mmol l-1 of G-6-P and 0.001% saponin. Still no effect of G-6-P on glucose transport could be detected. In contrast, the rate of D-glucose transport was affected, when extravesicular pH was varied from 6.0 to 7.8. The maximum glucose transport rate was found at pH 7.2 and was decreased at both higher and lower pH. It is concluded that G-6-P has no effect on GLUT4 intrinsic activity in rat skeletal muscle plasma membrane. In contrast, GLUT4 intrinsic activity is sensitive to changes in pH.

Animals↗
PubMed1994

Kinetics of lactate transport in sarcolemmal giant vesicles obtained from human skeletal muscle.

We developed a method that allows the measurement of muscle lactate transport in humans. The transport studies were carried out with giant (1.8- to 36-microns-diam) sarcolemmal vesicles obtained by collagenase treatment of needle biopsy material. Marker enzyme analyses demonstrated that the vesicular membrane is predominantly of sarcolemmal origin, contamination with sarcoplasmic reticulum membranes is very low, and mitochondrial membranes are not a major contaminant. The vesicles were loaded with labeled lactate, and the efflux was measured. The system displayed saturation kinetics and inhibitor sensitivity. In equilibrium exchange experiments (pH 7.4, 21 degrees C), the Michaelis-Menten constant (Km) for the carrier-mediated flux was 30 +/- 8 (SD) mM and maximal transport rate (Vmax) was 184 +/- 24 pmol.cm-2.s-1 (142 nmol.mg protein-1.min-1). In zero-trans efflux experiments, Km was 24 +/- 8 mM and Vmax was 81 +/- 11 pmol.cm-2.s-1 (63 nmol.mg protein-1.min-1). In infinite-cis experiments with a variable lactate concentration on the outside of the vesicles, Km was 8 +/- 4 mM and Vmax was 136 +/- 9 pmol.cm-2.s-1 (105 nmol.mg protein-1.min-1). Thus, the system displayed transacceleration. Low pH (6.4) had no significant effect on equilibrium exchange experiments, whereas in zero-trans experiments low pH at the trans side inhibited the flux by 50%. We concluded that lactate transport can be studied in giant vesicles obtained from a single human muscle biopsy. Our data provide evidence for the existence of a lactate carrier in human sarcolemma. This transport system must be taken into account in models of human lactate kinetics.

Adult↗
PubMed1994

Lactate transport studied in sarcolemmal giant vesicles from human muscle biopsies: relation to training status.

The present study examined sarcolemmal lactate transport capacity in humans of widely different training status. Muscle biopsies were obtained from m. vastus lateralis in 39 subjects divided into untrained (n = 13), trained (n = 7), and athlete [sprint runners (n = 2), endurance runners (n = 5), triathletes (n = 3), and road (n = 6) and track (n = 3) bicyclists] groups. From the biopsy sample giant vesicles were produced with collagenase treatment to determine the sarcolemmal lactate transport capacity, and histochemical analyses were made. The athletes had a higher capacity to transport lactate than the untrained and trained subjects (P < 0.01). Within the group of athletes, the bicyclists had a higher lactate transport capacity than the runners (P < 0.05), whereas there was no difference among trained subjects, runners, and triathletes. The lactate transport capacity was related to the occurrence of type I muscle fibers (r = 0.48, P < 0.01). The present results suggest that the capacity to transport lactate is higher in athletes than in untrained and less trained subjects. It might indicate that lactate transport capacity in human skeletal muscle can be changed by a high volume of training including frequent high-intensity sessions. In addition, sarcolemmal lactate transport capacity appears to be related to the fiber type distribution of a muscle.

Adult↗
PubMed1993

Lactate transport studied in sarcolemmal giant vesicles from rats: effect of training.

The effect of training on lactate transport capacity was studied in giant vesicles obtained with collagenase treatment of rat skeletal muscles. Marker enzyme analyses demonstrated that these vesicles are predominantly of sarcolemmal origin. Treadmill training induced significant adaptations in the capacity of rat skeletal muscles to transport lactate but swimming [low-intensity training, approximately 50% of maximal oxygen consumption (VO2 max)] did not. After 7 wk of moderate (90% of VO2max)- and high-intensity (112% of VO2max) interval treadmill training the carrier-mediated equilibrium exchange flux with 30 mM lactate was increased by 58 and 76%, respectively. During 5 wk of detraining the capacity to transport lactate decreased to near control level. It is concluded that physical training can increase the capacity to transport lactate in rat skeletal muscles and that the training intensity is of great importance. The adaptation appears to include both an increased number of transport proteins and a higher affinity of the individual transporters.

Animals↗
PubMed1991

Muscle lactate transport studied in sarcolemmal giant vesicles.

Lactate transport was studied in giant (median diameter 6.3 microns) sarcolemmal vesicles obtained by collagenase treatment of rat skeletal muscle. The lactate transport displayed stereospecificity, had a high temperature coefficient, and could be inhibited up to 90% with known transport inhibitors (PCMBS and cinnamate). In equilibrium exchange experiments, the L-lactate flux demonstrated saturation kinetics with Km = 23.7 mM and Vmax = 108 pmol cm-2 s-1. With lactate present on only one side of the membrane, (zero trans conditions), Vmax was reduced to 48 pmol cm-2 s-1. The flux rate displayed transacceleration. The lactate flux was coupled to a parallel H+ flux. Under equilibrium exchange conditions, the carrier-mediated lactate flux was not pH-dependent. In the zero trans experiments, H+ on the trans side acted as an inhibitor. The loaded form of the carrier reorients faster than the unloaded form, and the protonated form with no lactate bound reorients slowly or is immobile. When compared to intact muscles, the giant sarcolemmal vesicles retain their transport characteristics both qualitatively and quantitatively.

Animals↗
PubMed1991

Muscle lactate transport studied in sarcolemmal giant vesicles: dependence on fibre type and age.

Lactate transport was studied in sarcolemmal giant vesicles obtained from rat or rabbit skeletal muscle. With this technique it is possible to obtain quantitative information on sarcolemmal transport characteristics. In equilibrium exchange experiments with 10, 30 and 60 mM lactate, vesicles from 'red' rat muscles had a 50% higher lactate transport capacity than vesicles from 'white' muscles. Giant vesicles made from rabbit red muscles had a 39% higher lactate transport capacity than vesicles from white muscles. These differences probably reflect a different number of lactate transporters, whereas the lactate affinity in red and white muscles are identical. Lactate transport capacity decreased with age. Sarcolemmal giant vesicles made from 22-month-old rats had a 28% lower transport capacity than vesicles from 2-month old rats. In absolute terms, the initial exchange flux with 30 mM lactate was 92 and 127 pmol cm-2 sec-1 for old and young rats, respectively. In supplementary studies in which microelectrode measurements were made in single mouse muscle fibers, it was shown that the cellular acidification rate due to lactate incubation, was 38% lower in fibres from 18-month old mice than in fibres from 2-month old mice.

Aging↗
PubMed1990

Lactate and potassium fluxes from human skeletal muscle during and after intense, dynamic, knee extensor exercise.

This study examines lactate and K+ fluxes from muscle to blood during and after intense exercise. Ten men performed exhaustive dynamic exercise (mean load 65 W, mean duration 3.18 min) with the knee extensors of one leg. The mean lactate efflux was 15.5 (range 8.9-24.0) mmol min-1 at exhaustion, and it was linearly related to the lactate gradient. A linear relationship was also obtained if the H+ gradient was taken into account. Muscle pH decreased from 7.14 at rest to 6.71 (range 6.50-6.87) at exhaustion. At rest and during late recovery blood lactate was distributed across the erythrocyte membrane according to the membrane potential (intra-/extracellular ratio of 0.5), but during rapid lactate release this ratio decreased to 0.2. In-vitro experiments demonstrated a time constant of 1.2 min for lactate efflux from the erythrocytes. Approximately 70% of the K+ ions released from the muscle to the blood accumulated in the plasma; the rest were taken up by other tissues. However, erythrocytes were not involved as a dilution space. The small change in erythrocyte K+ concentration was due to cellular volume changes. During recovery the kinetics of K+ reuptake by the muscle were described by a very fast (less than 1 min) and a slow component (greater than 1 min): the magnitude of the former was equivalent to what had accumulated in the plasma. Individuals displayed a wide range of intramuscular lactate concentrations and pH values at exhaustion. Further, the pH changes were not as extreme as previously reported, suggesting that pH may not be the only factor involved in the fatigue process. A possible role for the potassium shifts as a limiting factor for muscle function is discussed.

Adult↗