Intracellular Acidosis Enhances the Excitability of Working Muscle

Pedersen, Thomas Klit; Nielsen, Ole Bækgaard; Lamb, Graham D.; Stephenson, D. George

doi:10.1126/science.1101141

Cited by 256 publications

(262 citation statements)

References 17 publications

Supporting

Mentioning

244

Contrasting

Unclassified

Order By: Relevance

“…leg exercise) via an increase in blood lactate (up to 10 mmol l ¡1 ), resulting in reduced performance (Bangsbo et al 1996;Hogan and Welch 1984;Jacobs et al 1993). However, recent studies have shown that muscle performance is enhanced rather than impaired by higher lactate concentrations (Nielsen et al 2001;Pedersen et al 2004). Moreover, in a previous study we did not observe a signiWcant increase in blood lactate concentration as a result of inspiratory resistive breathing at 70% PI max to exhaustion (Rohrbach et al 2003).…”

Section: Methodological Aspectsmentioning

confidence: 76%

Expiratory muscle fatigue impairs exercise performance

et al. 2007

View full text Add to dashboard Cite

High-intensity, exhaustive exercise may lead to inspiratory as well as expiratory muscle fatigue (EMF). Induction of inspiratory muscle fatigue (IMF) before exercise has been shown to impair subsequent exercise performance. The purpose of the present study was to determine whether induction of EMF also aVects subsequent exercise performance. Twelve healthy young men performed Wve 12-min running tests on a 400-m track on separate days: a preliminary trial, two trials after induction of EMF, and two trials without prior muscle fatigue. Tests with and without prior EMF were performed in an alternate order, randomly starting with either type. EMF was deWned as a ¸20% drop in maximal expiratory mouth pressure achieved during expiratory resistive breathing against 50% maximal expiratory mouth pressure. The average distance covered in 12 min was signiWcantly smaller during exercise with prior EMF compared to control exercise (2872 § 256 vs. 2957 § 325 m; P = 0.002). Running speed was consistently lower (0.13 m s ¡1 ) throughout the entire 12 min of exercise with prior EMF. A signiWcant correlation was observed between the level of EMF (decrement in maximal expiratory mouth pressure after resistive breathing) and the reduction in running distance (r 2 = 0.528, P = 0.007). Perceived respiratory exertion was higher during the Wrst 800 m and heart rate was lower throughout the entire test of running with prior EMF compared to control exercise (5.3 § 1.6 vs. 4.5 § 1.7 points, P = 0.002; 173 § 10 vs. 178 § 7 beats min ¡1 , P = 0.005). We conclude that EMF impairs exercise performance as previously reported for IMF.

show abstract

Section: Methodological Aspectsmentioning

confidence: 76%

Expiratory muscle fatigue impairs exercise performance

et al. 2007

View full text Add to dashboard Cite

show abstract

“…For now, the 'muscular' investigators are ahead of the 'brainy' ones, at least where the clarity of the glycolytic picture is concerned. Recently, members of the first group shot down another 'white elephant,' showing that lactate is not the cause of muscle fatigue (Pedersen et al, 2004). The hypothesis put forward here postulates that lactate is the major product of cerebral (and other tissues) glycolysis, whether aerobic or anaerobic, neuronal or astrocytic.…”

Section: Resultsmentioning

confidence: 90%

Lactate: The Ultimate Cerebral Oxidative Energy Substrate?

Schurr

2006

J Cereb Blood Flow Metab

265

236

View full text Add to dashboard Cite

Research over the past two decades has renewed the interest in lactate, no longer as a useless end product of anaerobic glycolysis in brain (and other tissues), but as an oxidative substrate for energy metabolism. While this topic would be considered blasphemy only three decades ago, much recent evidence indicates that lactate does play a major role in aerobic energy metabolism in the brain, the heart, skeletal muscle, and possibly in any other tissue and organ. Nevertheless, this concept has challenged the old dogma and ignited a fierce debate, especially among neuroscientists, pitting the supporters of glucose as the major oxidative energy substrate against those who support lactate as a possible alternative to glucose under certain conditions. Meanwhile, researchers working on energy metabolism in skeletal muscle have taken great strides toward bridging between these two extreme positions, while avoiding the high decibels of an emotional debate. Employing their findings along with the existing old and new data on cerebral energy metabolism, it is postulated here that lactate is the only major product of cerebral (and other tissues) glycolysis, whether aerobic or anaerobic, neuronal or astrocytic, under rest or during activation. Consequently, this postulate entails that lactate is a major, if not the only, substrate for the mitochondrial tricarboxylic acid cycle. If proven true, this hypothesis could provide better understanding of the biochemistry and physiology of (cerebral) energy metabolism, while holding important implications in the field of neuroimaging. Concomitantly, it could satisfy both 'glucoseniks' and 'lactatians' in the ongoing debate.

show abstract

“…Skeletal muscle acidification leads to decreased sarcolemmal chloride conductance, which acts to maintain excitability of the partially depolarized sarcolemma and opposes the effect of muscle fatigue (4,5). However, studies of the pH dependence of heterologously expressed ClC-1 have failed to reconcile this decreased chloride conductance with a direct effect of protons on ClC-1 (28,53,54).…”

Section: Discussionmentioning

confidence: 99%

“…With intense activity, however, accumulation of extracellular K ϩ leads to partial membrane depolarization and chronic inactivation of voltage-dependent Na ϩ channels (3). Concurrently, acidification of the muscle leads to decreased chloride conductance, reducing the shunting effect and thereby reducing the magnitude of Na ϩ current required to excite the muscle membrane (4,5). The molecular mechanism underlying the reduction of muscle chloride conductance with acidification appears to be strong potentiation of ClC-1 inhibition by intracellular ATP at low pH (6,7).…”

mentioning

confidence: 99%

Intracellular β-Nicotinamide Adenine Dinucleotide Inhibits the Skeletal Muscle ClC-1 Chloride Channel

Bennetts

Chen

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Weakly voltage-dependent ClC-1 chloride channels regulate skeletal muscle excitability. Results: Intracellular NAD(H) altered the voltage dependence of ClC-1 gating, and specific mutations attenuated this effect. Conclusion: NAD(H) directly inhibits ClC-1 chloride channels by binding to intracellular domains. Significance: ClC-1 inhibition by NAD(H) may play an important role in muscle fatigue and the pathophysiology of myotonia congenita.

show abstract

Intracellular Acidosis Enhances the Excitability of Working Muscle

Cited by 256 publications

References 17 publications

Expiratory muscle fatigue impairs exercise performance

Expiratory muscle fatigue impairs exercise performance

Lactate: The Ultimate Cerebral Oxidative Energy Substrate?

Intracellular β-Nicotinamide Adenine Dinucleotide Inhibits the Skeletal Muscle ClC-1 Chloride Channel

Contact Info

Product

Resources

About