Importance of pH regulation and lactate/H+ transport capacity for work production during supramaximal exercise in humans

2007 ◽  
Vol 102 (5) ◽  
pp. 1936-1944 ◽  
Author(s):  
Laurent Messonnier ◽  
Michael Kristensen ◽  
Carsten Juel ◽  
Christian Denis

We examine the influence of the cytosolic and membrane-bound contents of carbonic anhydrase (CA; CAII, CAIII, CAIV, and CAXIV) and the muscle content of proteins involved in lactate and proton transport [monocarboxylate transporter (MCT) 1, MCT4, and Na+/H+ exchanger 1 (NHE1)] on work capacity during supramaximal exercise. Eight healthy, sedentary subjects performed exercises at 120% of the work rate corresponding to maximal oxygen uptake (Ẇmax) until exhaustion in placebo (Con) and metabolic alkalosis (Alk) conditions. The total (Wtot) and supramaximal work performed (Wsup) was measured. Muscle biopsies were obtained before and immediately after standardized exercises (se) at 120% Ẇmax in both conditions to determine the content of the targeted proteins, the decrease in muscle pH (ΔpHm), and the muscle lactate accumulation ([Lac]m) per joule of Wsup (ΔpHm/Wsup-se and Δ[Lac]m/Wsup-se, respectively) and the dynamic buffer capacity. In Con, Wsup was negatively correlated with ΔpHm/Wsup-se, positively correlated with Δ[Lac]m/Wsup-se and MCT1, and tended to be positively correlated with MCT4 and NHE1. CAII + CAIII were correlated positively with ΔpHm/Wsup-se and negatively with Δ[Lac]m/Wsup-se, while CAIV was positively related to Wtot. The changes in Wsup with Alk were correlated positively with those in dynamic buffer capacity and negatively with Wsup in Con. Performance improvement with Alk was greater in subjects having a low content of proteins involved in pH regulation and lactate/proton transport. These results show the importance of pH regulating mechanisms and lactate/proton transport on work capacity and the role of the CA to delay decrease in pHm and accumulation in [Lac]m during supramaximal exercise in humans.

1998 ◽  
Vol 274 (3) ◽  
pp. E554-E559 ◽  
Author(s):  
Henriette Pilegaard ◽  
Sven Asp

The effect of prior eccentric contractions on skeletal muscle lactate/H+transport was investigated in rats. Lactate transport was measured in sarcolemmal giant vesicles obtained from soleus and red (RG) and white gastrocnemii (WG) muscles 2 days after intense eccentric contractions (ECC) and from the corresponding contralateral control (CON) muscles. The physiochemical buffer capacity was determined in the three muscle types from both ECC and CON legs. Furthermore, the effect of prior eccentric contractions on release and muscle content of lactate and H+ during and after supramaximal stimulation was examined using the perfused rat hindlimb preparation. The lactate transport rate was lower ( P < 0.05) in vesicles obtained from ECC-WG (29%) and ECC-RG (13%) than in vesicles from the CON muscles. The physiochemical buffer capacity was reduced ( P < 0.05) in ECC-WG (13%) and ECC-RG (9%) compared with the corresponding CON muscles. There were only marginal effects on the soleus muscle. Muscle lactate concentrations and release of lactate during recovery from intense isometric contractions were lower ( P< 0.05) in ECC than in CON hindlimbs, indicating decreased anaerobic glycogenolysis. In conclusion, the sarcolemmal lactate/H+ transport capacity and the physiochemical buffer capacity were reduced in prior eccentrically stimulated WG and RG in rats, suggesting that muscle pH regulation may be impaired after unaccustomed eccentric exercise. In addition, the data indicate that the glycogenolytic potential is decreased in muscles exposed to prior eccentric contractions.


2013 ◽  
Vol 305 (7) ◽  
pp. R811-R821 ◽  
Author(s):  
Thomas P. Gunnarsson ◽  
Peter M. Christensen ◽  
Martin Thomassen ◽  
Lars R. Nielsen ◽  
Jens Bangsbo

The effects of intensified training in combination with a reduced training volume on muscle ion kinetics, transporters, and work capacity were examined. Eight well-trained cyclists replaced their regular training with speed-endurance training (12 × 30 s sprints) 2–3 times per week and aerobic high-intensity training (4–5 × 3–4 min at 90–100% of maximal heart rate) 1–2 times per week for 7 wk and reduced training volume by 70% (intervention period; IP). The duration of an intense exhaustive cycling bout (EX2; 368 ± 6 W), performed 2.5 min after a 2-min intense cycle bout (EX1), was longer ( P < 0.05) after than before IP (4:16 ± 0:34 vs. 3:37 ± 0:28 min:s), and mean and peak power during a repeated sprint test improved ( P < 0.05) by 4% and 3%, respectively. Femoral venous K+ concentration in recovery from EX1 and EX2 was lowered ( P < 0.05) after compared with before IP, whereas muscle interstitial K+ concentration and net muscle K+ release during exercise was unaltered. No changes in muscle lactate and H+ release during and after EX1 and EX2 were observed, but the in vivo buffer capacity was higher ( P < 0.05) after IP. Expression of the ATP-sensitive K+ (KATP) channel (Kir6.2) decreased by IP, with no change in the strong inward rectifying K+ channel (Kir2.1), muscle Na+-K+ pump subunits, monocarboxylate transporters 1 and 4 (MCT1 and MCT4), and Na+/H+ exchanger 1 (NHE1). In conclusion, 7 wk of intensified training with a reduced training volume improved performance during repeated intense exercise, which was associated with a greater muscle reuptake of K+ and muscle buffer capacity but not with the amount of muscle ion transporters.


1996 ◽  
Vol 271 (1) ◽  
pp. E38-E43 ◽  
Author(s):  
A. Casey ◽  
D. Constantin-Teodosiu ◽  
S. Howell ◽  
E. Hultman ◽  
P. L. Greenhaff

Nine male subjects performed two bouts of 30-s maximal isokinetic cycling. Each bout of exercise was performed at 80 revolutions/min and was separated by 4 min of recovery. Mixed-muscle phosphocreatine (PCr) resynthesis during recovery (88.1 +/- 6.1%) was positively correlated with the restoration of total work production during bout 2 (r = 0.80, P < 0.05). During bout 1, ATP and PCr utilization were greater in type II compared with type I fibers (P < 0.01 and P < 0.05, respectively). The subsequent 4-min period of recovery was insufficient to allow total restoration of ATP and PCr in type II fibers, but restoration of ATP and PCr in type I fibers was almost complete. During the second bout of exercise, ATP and PCr utilization were reduced in type II fibers (P < 0.01), without a corresponding change in type I fibers, and performance was also significantly reduced. The reduction in work capacity observed during bout 2 may have been related to a slower resynthesis, and consequently a reduced availability, of ATP and PCr in type II fibers.


1985 ◽  
Vol 69 (5) ◽  
pp. 505-510 ◽  
Author(s):  
E. Hultman ◽  
S. Del Canale ◽  
H. Sjöholm

1. Five volunteers were studied before and after oral administration of NH4Cl (0.3 g/kg body wt.) given in order to create a moderate acidosis. 2. The quadriceps femoris muscles were stimulated electrically for 75 s and muscle biopsies for determination of pH and metabolite content were taken before, at the end of contraction and after 10 min in the recovery period. 3. Muscle pH at rest (mean 7.04) was not significantly decreased after acidification despite an extracellular pH decrease of 0.15 unit. 4. After contraction muscle pH was significantly lower after NH4Cl. Mean values before and after acidification were 6.70 and 6.54 respectively. 5. The buffer capacity calculated as the total capacity of the muscle to buffer H+ produced during the isometric contraction before and after NH4Cl ingestion was reduced from 68.6 sl to 54.5 sl. 6. The force produced by contracting muscle was significantly lower at the end of the contraction period after NH4Cl ingestion, 44.6% of initial compared with 55.4% without NH4Cl.


2006 ◽  
Vol 291 (3) ◽  
pp. E566-E573 ◽  
Author(s):  
Robert S. Lee-Young ◽  
Matthew J. Palmer ◽  
Kelly C. Linden ◽  
Kieran LePlastrier ◽  
Benedict J. Canny ◽  
...  

There is evidence that increasing carbohydrate (CHO) availability during exercise by raising preexercise muscle glycogen levels attenuates the activation of AMPKα2 during exercise in humans. Similarly, increasing glucose levels decreases AMPKα2 activity in rat skeletal muscle in vitro. We examined the effect of CHO ingestion on skeletal muscle AMPK signaling during exercise in nine active male subjects who completed two 120-min bouts of cycling exercise at 65 ± 1% V̇o2 peak. In a randomized, counterbalanced order, subjects ingested either an 8% CHO solution or a placebo solution during exercise. Compared with the placebo trial, CHO ingestion significantly ( P < 0.05) increased plasma glucose levels and tracer-determined glucose disappearance. Exercise-induced increases in muscle-calculated free AMP (17.7- vs. 11.8-fold), muscle lactate (3.3- vs. 1.8-fold), and plasma epinephrine were reduced by CHO ingestion. However, the exercise-induced increases in skeletal muscle AMPKα2 activity, AMPKα2 Thr172 phosphorylation and acetyl-CoA Ser222 phosphorylation, were essentially identical in the two trials. These findings indicate that AMPK activation in skeletal muscle during exercise in humans is not sensitive to changes in plasma glucose levels in the normal range. Furthermore, the rise in plasma epinephrine levels in response to exercise was greatly suppressed by CHO ingestion without altering AMPK signaling, raising the possibility that epinephrine does not directly control AMPK activity during muscle contraction under these conditions in vivo.


1995 ◽  
Vol 269 (3) ◽  
pp. E458-E468 ◽  
Author(s):  
C. T. Putman ◽  
N. L. Jones ◽  
L. C. Lands ◽  
T. M. Bragg ◽  
M. G. Hollidge-Horvat ◽  
...  

The regulation of the active form of pyruvate dehydrogenase (PDHa) and related metabolic events were examined in human skeletal muscle during repeated bouts of maximum exercise. Seven subjects completed three consecutive 30-s bouts of maximum isokinetic cycling, separated by 4 min of recovery. Biopsies of the vastus lateralis were taken before and immediately after each bout. PDHa increased from 0.45 +/- 0.15 to 2.96 +/- 0.38, 1.10 +/- 0.11 to 2.91 +/- 0.11, and 1.28 +/- 0.18 to 2.82 +/- 0.32 mmol.min-1.kg wet wt-1 during bouts 1, 2, and 3, respectively. Glycolytic flux was 13-fold greater than PDHa in bouts 1 and 2 and 4-fold greater during bout 3. This discrepancy between the rate of pyruvate production and oxidation resulted in substantial lactate accumulation to 89.5 +/- 11.6 in bout 1, 130.8 +/- 13.8 in bout 2, and 106.6 +/- 10.1 mmol/kg dry wt in bout 3. These events coincided with an increase in the mitochondrial oxidation state, as reflected by a fall in mitochondrial NADH/NAD, indicating that muscle lactate production during exercise was not an O2-dependent process in our subjects. During exercise the primary factor regulating PDHa transformation was probably intracellular Ca2+. In contrast, the primary regulatory factors causing greater PDHa during recovery were lower ATP/ADP and NADH/NAD and increased concentrations of pyruvate and H+. Greater PDHa during recovery facilitated continued oxidation of the lactate load between exercise bouts.


1988 ◽  
Vol 255 (3) ◽  
pp. R513-R519 ◽  
Author(s):  
G. P. Dobson ◽  
W. S. Parkhouse ◽  
J. M. Weber ◽  
E. Stuttard ◽  
J. Harman ◽  
...  

The aim of this study was to examine some metabolic properties and changes that occur in skeletal muscle and blood of greyhounds after an 800-m sprint. Three prime moving fast-twitch muscles were selected: biceps femoris (BF), gastrocnemius (G), and vastus lateralis (VL). The amount of glycogen utilized during the event was 42.57, 43.86, and 42.73 mumol glucosyl units/g wet wt, respectively. Expressed as a function of race time (48.3 +/- 0.7 s, n = 3), the mean rate of glycogen breakdown was 53.48 +/- 0.5 mumol.g wet wt-1.min-1 during the sprint. This is equivalent to an ATP turnover of 160 mumol.g wet wt-1.min-1, assuming 100% anaerobic conversion to lactate. This represents a conservative estimate, since greyhound muscle is heterogeneous and comprised of a large percentage of fast-twitch oxidative fibers (Armstrong et al., Am. J. Anat. 163: 87-98, 1982). The large decrease in muscle glycogen was accompanied by a 6- to 7-fold increase in muscle lactate from 3.48 +/- 0.13 to 25.42 +/- 3.54 (BF), 2.54 +/- 1.05 to 18.96 +/- 2.60 (G), and 4.57 +/- 0.44 to 30.09 +/- 1.94 mumol.g wet wt (VL), and a fall in muscle pH from 6.88 +/- 0.03 to 6.40 +/- 0.02 (BF), 6.92 +/- 0.02 to 6.56 +/- 0.02 (G), and 6.93 +/- 0.02 to 6.47 +/- 0.01 (VL). Cytosolic phosphorylation potential in BF decreased 10-fold from 11,360 +/- 680 to 1,184 +/- 347, and redox potential decreased 5-fold, indicating a marked reduction in the cytosol at this time.(ABSTRACT TRUNCATED AT 250 WORDS)


2008 ◽  
Vol 294 (2) ◽  
pp. R594-R600 ◽  
Author(s):  
H. J. Green ◽  
T. A. Duhamel ◽  
G. P. Holloway ◽  
J. W. Moule ◽  
D. W. Ranney ◽  
...  

In this study, we have investigated the hypothesis that an exercise protocol designed to repeatedly induce a large dependence on carbohydrate and large increases in glycolytic flux rate would result in rapid increases in the principal glucose and lactate transporters in working muscle, glucose transporter (GLUT)-4 and monocarboxylate transporter (MCT)4, respectively, and in activity of hexokinase (Hex), the enzyme used to phosphorylate glucose. Transporter abundance and Hex activity were assessed in homogenates by Western blotting and quantitative chemiluminescence and fluorometric techniques, respectively, in samples of tissue obtained from the vastus lateralis in 12 untrained volunteers [peak aerobic power (V̇o2peak) = 44.3 ± 2.3 ml·kg−1·min−1] before cycle exercise at repetitions 1 (R1), 2 (R2), 9 (R9), and 16 (R16). The 16 repetitions of the exercise were performed for 6 min at ∼90% V̇o2peak, once per hour. Compared with R1, GLUT-4 increased ( P < 0.05) by 28% at R2 and remained elevated ( P < 0.05) at R9 and R16. For MCT-4, increases ( P < 0.05) of 24% were first observed at R9 and persisted at R16. No changes were observed in GLUT-1 and MCT-1 or in Hex activity. The ∼17- to 24-fold increase ( P < 0.05) in muscle lactate observed at R1 and R2 was reduced ( P < 0.05) to an 11-fold increase at R9 and R16. It is concluded that an exercise protocol designed to strain muscle carbohydrate reserves and to result in large increases in lactic acid results in a rapid upregulation of both GLUT-4 and MCT-4.


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