Determinants of surface membrane and transverse-tubular excitability in skeletal muscle: implications for high-intensity exercise

2005 ◽  
Vol 2 (4) ◽  
pp. 209-217 ◽  
Author(s):  
Michael I. Lindinger

AbstractThe fatigue of high-intensity exercise is now believed to reside primarily within the excitation–contraction coupling processes associated with the plasma membrane of skeletal muscle (sarcolemm) and calcium-mediated events leading to myofilament sliding. This paper summarizes recent developments and advances in the identification of factors that contribute to changes in sarcolemmal excitability of mammalian skeletal muscle as a consequence of high-intensity exercise. There is an increasing recognition of the probable role that is played by the transverse tubular system (T-system), a system that comprises c. 80% of the total sarcolemmal surface capable of ion exchange. Furthermore, the fluid within the T-system has limited access to interstitial fluid bathing myofibres; hence, T-system fluid is probably markedly different from interstitial fluid during high-intensity exercise. Mechanically skinned fibre preparation is providing many new insights into functions of the surface membrane and T-system in fatigue. A scenario is developed whereby accumulation of potassium within the T-system ([K+]o) contributes to reduced membrane excitability, as well as lowering of T-system sodium and chloride, concomitant with loss of intracellular potassium ([K+]i) and accumulation of intracellular sodium ([Na+]) and chloride ([Cl−]). Lowering the [Na+]o/[Na+]i ratio and raising myoplasmic [Na+]i have been shown to decrease membrane excitability and impair action potential propagation. Maintained high [Cl−]o may also have a protective effect in maintaining membrane excitability, and this effect appears to be very pronounced in the presence of raised [K+]o. In contrast to dogma associating high [H+] to fatigue, recent studies have also shown that induced acidosis that results in increased [H+]o and [H+]i restores force production in muscles and skinned fibres fatigued by intermittent tetanic stimulation. This effect may be due to a decrease in surface membrane Cl− permeability that serves to restore membrane excitability. During high-intensity exercise, simultaneous changes in trans-membrane ion concentrations and membrane ion conductances may serve to reduce impairment of membrane excitability that provides for a maintained, though reduced, contractile function.

1995 ◽  
Vol 20 (3) ◽  
pp. 357-368 ◽  
Author(s):  
Michael I. Lindinger

This brief review describes the main physicochemical factors that contribute to increases in intracellular hydrogen ion concentration ([H+]i) in mammalian skeletal muscle during high intensity exercise. High intensity exercise results in changes in the three main independent physicochemical variables: PCO2, the strong ion difference ([SID]), and total concentration of weak acids and bases ([Atot]), within the intracellular fluid compartment of contracting muscle that result in increased [H+]i. The decrease in [SID] contributes 62% to the increase in [H+]i, due to decreased [K+]i and increased [lactate]i; the decrease in phosphocreatine ([PCr2−]i) exerts an alkalinizing effect. The increase in [Atot], resulting primarily from increases in inorganic phosphate and creatine as a result of PCr2− breakdown, contributes 19% to the increase in [H+]i. An increase in the apparent proton dissociation constant (KA) for [Atot] contributes 7% to the increase in [H+]i. PCO2 is a relatively poor effector of changes in [H+]i, such that a 50-mmHg increase in PCO2 contributes only 12% to the increase in [H+]i during high intensity exercise. Key words: acid-base balance, strong ion difference, phosphocreatine, potassium, carbon dioxide, metabolism


2018 ◽  
Vol 50 (12) ◽  
pp. 2409-2417 ◽  
Author(s):  
GWENAEL LAYEC ◽  
GREGORY M. BLAIN ◽  
MATTHEW J. ROSSMAN ◽  
SONG Y. PARK ◽  
COREY R. HART ◽  
...  

2017 ◽  
Vol 595 (20) ◽  
pp. 6379-6380 ◽  
Author(s):  
Tharmegan Tharmaratnam ◽  
Tyler Tabobondung ◽  
Taylor Tabobondung ◽  
Seyon Sivagurunathan ◽  
Mina Amin Iskandar

2018 ◽  
Vol 315 (5) ◽  
pp. E1034-E1045 ◽  
Author(s):  
Kristoffer Svensson ◽  
Jessica R. Dent ◽  
Shahriar Tahvilian ◽  
Vitor F. Martins ◽  
Abha Sathe ◽  
...  

The pyruvate dehydrogenase complex (PDC) converts pyruvate to acetyl-CoA and is an important control point for carbohydrate (CHO) oxidation. However, the importance of the PDC and CHO oxidation to muscle metabolism and exercise performance, particularly during prolonged or high-intensity exercise, has not been fully defined especially in mature skeletal muscle. To this end, we determined whether skeletal muscle-specific loss of pyruvate dehydrogenase alpha 1 ( Pdha1), which is a critical subunit of the PDC, impacts resting energy metabolism, exercise performance, or metabolic adaptation to high-fat diet (HFD) feeding. For this, we generated a tamoxifen (TMX)-inducible Pdha1 knockout (PDHmKO) mouse, in which PDC activity is temporally and specifically ablated in adult skeletal muscle. We assessed energy expenditure, ex vivo muscle contractile performance, and endurance exercise capacity in PDHmKO mice and wild-type (WT) littermates. Additionally, we studied glucose homeostasis and insulin sensitivity in muscle after 12 wk of HFD feeding. TMX administration largely ablated PDHα in skeletal muscle of adult PDHmKO mice but did not impact energy expenditure, muscle contractile function, or low-intensity exercise performance. Additionally, there were no differences in muscle insulin sensitivity or body composition in PDHmKO mice fed a control or HFD, as compared with WT mice. However, exercise capacity during high-intensity exercise was severely impaired in PDHmKO mice, in parallel with a large increase in plasma lactate concentration. In conclusion, although skeletal muscle PDC is not a major contributor to resting energy expenditure or long-duration, low-intensity exercise performance, it is necessary for optimal performance during high-intensity exercise.


2018 ◽  
Vol 40 (01) ◽  
pp. 16-22 ◽  
Author(s):  
Alberto Pérez-López ◽  
Marcos Martin-Rincon ◽  
Alfredo Santana ◽  
Ismael Perez-Suarez ◽  
Cecilia Dorado ◽  
...  

AbstractInterleukin (IL)-15 stimulates mitochondrial biogenesis, fat oxidation, glucose uptake and myogenesis in skeletal muscle. However, the mechanisms by which exercise triggers IL-15 expression remain to be elucidated in humans. This study aimed at determining whether high-intensity exercise and exercise-induced RONS stimulate IL-15/IL-15Rα expression and its signaling pathway (STAT3) in human skeletal muscle. Nine volunteers performed a 30-s Wingate test in normoxia and hypoxia (PIO2=75 mmHg), 2 h after placebo or antioxidant administration (α-lipoic acid, vitamin C and E) in a randomized double-blind design. Blood samples and muscle biopsies (vastus lateralis) were obtained before, immediately after, and 30 and 120 min post-exercise. Sprint exercise upregulated skeletal muscle IL-15 protein expression (ANOVA, P=0.05), an effect accentuated by antioxidant administration in hypoxia (ANOVA, P=0.022). In antioxidant conditions, the increased IL-15 expression at 120 min post-exercise (33%; P=0.017) was associated with the oxygen deficit caused by the sprint (r=–0.54; P=0.020); while, IL-15 and Tyr705-STAT3 AUCs were also related (r=0.50; P=0.036). Antioxidant administration promotes IL-15 protein expression in human skeletal muscle after sprint exercise, particularly in severe acute hypoxia. Therefore, during intense muscle contraction, a reduced PO2 and glycolytic rate, and possibly, an attenuated RONS generation may facilitate IL-15 production, accompanied by STAT3 activation, in a process that does not require AMPK phosphorylation.


2019 ◽  
Vol 44 (12) ◽  
pp. 1391-1394
Author(s):  
Martin J. MacInnis ◽  
Lauren E. Skelly ◽  
F. Elizabeth Godkin ◽  
Brian J. Martin ◽  
Thomas R. Tripp ◽  
...  

The legs of 9 men (age 21 ± 2 years, 45 ± 4 mL/(kg·min)) were randomly assigned to complete 6 sessions of high-intensity exercise training, involving either one or four 5-min bouts of counterweighted, single-leg cycling. Needle biopsies from vastus lateralis revealed that citrate synthase maximal activity increased after training in the 4-bout group (p = 0.035) but not the 1-bout group (p = 0.10), with a significant difference between groups post-training (13%, p = 0.021). Novelty Short-term training using brief intense exercise requires multiple bouts per session to increase mitochondrial content in human skeletal muscle.


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