Michael J . McKenna | Victoria University (original) (raw)

Papers by Michael J . McKenna

The Journal of Physiology, Apr 23, 2017

Ageing is associated with an upregulation of mitochondrial dynamics proteins mitofusin 2 (Mfn2) a... more Ageing is associated with an upregulation of mitochondrial dynamics proteins mitofusin 2 (Mfn2) and mitochondrial dynamics protein 49 (MiD49) in human skeletal muscle with the increased abundance of Mfn2 being exclusive to type II muscle fibres. r These changes occur despite a similar content of mitochondria, as measured by COXIV, NDUFA9 and complexes in their native states (Blue Native PAGE). r Following 12 weeks of high-intensity training (HIT), older adults exhibit a robust increase in mitochondria content, while there is a decline in Mfn2 in type II fibres. r We propose that the upregulation of Mfn2 and MiD49 with age may be a protective mechanism to protect against mitochondrial dysfunction, in particularly in type II skeletal muscle fibres, and that exercise may have a unique protective effect negating the need for an increased turnover of mitochondria.

Frontiers in Physiology, Aug 2, 2016

The maintenance of transmembrane Na + and K + concentration gradients and membrane potential is v... more The maintenance of transmembrane Na + and K + concentration gradients and membrane potential is vital for the production of force in skeletal muscle. In aging an inability to maintain ion regulation and membrane potential would have adverse consequences on the capacity for performing repeated muscle contractions, which are critical for everyday activities and functional independence. This short review focusses on the effects of aging on one major and vital component affecting muscle Na + and K + concentrations, membrane potential and excitability in skeletal muscle, the Na + ,K + -ATPase (Na + ,K + -pump, NKA) protein. The review examines the effects of age on NKA in both human and rodent models and highlights a distant lack of research in NKA with aging. In rodents, the muscle NKA measured by [ 3 H]ouabain binding site content, declines with advanced age from peak values in early life. In human skeletal muscle, however, there appears to be no age effect on [ 3 H]ouabain binding site content in physically active older adults between 55 and 76 years compared to those aged between 18 and 30 years of age. Analysis of the NKA isoforms reveal differential changes with age in fiber-types in both rat and humans. The data show considerable disparities, suggesting different regulation of NKA isoforms between rodents and humans. Finally we review the importance of physical activity on NKA content in older humans. Findings suggest that physical activity levels of an individual may have a greater effect on regulating the NKA content in skeletal muscle rather than aging per se, at least up until 80 years of age. Keywords: age, Na + K + -pump, single fiber, [ 3 H]ouabain A fundamental factor underpinning skeletal muscle contractile function is the maintenance of membrane excitability, which is heavily dependent on transmembrane sodium (Na + ), potassium (K + ), and chloride (Cl -) gradients and conductance's via their effects on muscle membrane potential (E m ) . The intramuscular regulation of these ions is important in both the development of and preservation against muscle fatigue . Therefore, any disturbances in muscle ion regulation with aging are likely to impact adversely on cellular excitability and the capacity to undertake repeated muscle contractions, thereby affecting the capability to successfully complete simple daily tasks, and thus on quality of life. Preservation of muscle mass and function is critical in older individuals, due their greater risk of falls, and the consequential effects, that include ongoing physical disability,

Journal of Applied Physiology, Mar 1, 2002

Exercise Biochemistry Review, Oct 3, 2018

Objective Heat shock proteins (HSPs) are ubiquitously expressed proteins that help preserve cellu... more Objective Heat shock proteins (HSPs) are ubiquitously expressed proteins that help preserve cellular homeostasis. Within mammalian skeletal muscle three of the better characterised HSPs are HSP72, HSP27 and αB-crystallin. Among other roles, these three HSPs are involved in regulation of muscle mass and function and may be of importance in ageing. HSP's are fibre-type dependent in rat skeletal muscle and thus examining these proteins in humans should be completed on the single fibre level, particularly in ageing where maladaptations primarily occur in Type II fibres. High-Intensity Training (HIT) is a commonly used method to improve muscle health and function in the elderly, but HSP adaptability to training has not yet been investigated. Methods This study examined isolated single muscle fibre segments collected from freeze-dried vastus lateralis muscle samples from young (25 /-3 year old) and older (70 /-4 year old) healthy individuals. A further sample was collected from the older individuals following 12 weeks of HIT, where they performed 4 x 4 min @ ~90-95% of peak heart rate (HR), with 4 min active recovery at 50-60% peak HR Results Basal expression of HSP's in skeletal muscle: HSP70 tended to be higher in Type I fibres compared to Type II in young adults (p=0.08) and was higher in Type I compared to Type II fibres of older adults (p=0.03). HSP27 abundance was higher in Type I fibres compared to Type II in young adults (p=0.01) and tended to be higher in Type I compared to Type II fibres in older adults (p=0.07). The abundance of αβ-crystallin was more abundant in Type I fibres compared to Type II in both young and older adults (p<0.05). Preliminary data revealed that the abundance of pABCser59 and pHSP2782 displayed no fibre-type specific abundances in either young or older adults. Age effects on HSP's: There was no difference in the abundance of HSP70, HSP27, ABC or pHSP2782 between young and older adults in either Type I or Type II fibres. There was an increase in the abundance of pABCser59 in Type I fibres in older adults compared to Type I fibres of young adults (p=0.03), with no difference in Type II fibres. Effects of HIT on HSP's: HIT in the older individuals increased the abundance of HSP70 in Type I fibres (p<0.01) but not Type II. HIT tended to decrease the abundance of HSP27 in Type I fibres (0.92±0.66, p=0.06) and tended to increase the abundance of αβ-crystallin in Type I fibres (1.03±1.51 p=0.07). Conclusions These results revealed that in healthy, older individuals, the basal levels of HSP27, ABC or pHSP2782 are not different to those in young adults in either Type I or Type II fibres. This could indicate that the muscle from the older individuals was not compromised. Interestingly, in response to HIT there were varying changes between these HSP's, and of note these occurred only in Type I fibres. Given that during HIT Type II fibres would be activated to a greater extent, it appears that the recovery phases of the HIT were most responsive to HSPs.

This study investigated creatine supplementation (CrS) effects on muscle total creatine (TCr), cr... more This study investigated creatine supplementation (CrS) effects on muscle total creatine (TCr), creatine phosphate (CrP), and intermittent sprinting performance by using a design incorporating the time course of the initial increase and subsequent washout period of muscle TCr. Two groups of seven volunteers ingested either creatine [Cr; 6 ϫ (5 g Cr-H 2 O ϩ 5 g dextrose)/day)] or a placebo (6 ϫ 5 g dextrose/day) over 5 days. Five 10-s maximal cycle ergometer sprints with rest intervals of 180, 50, 20, and 20 s and a resting vastus lateralis biopsy were conducted before and 0, 2, and 4 wk after placebo or CrS. Resting muscle TCr, CrP, and Cr were unchanged after the placebo but were increased (P Ͻ 0.05) at 0 [by 22.9 Ϯ 4.2, 8.9 Ϯ 1.9, and 14.0 Ϯ 3.3 (SE) mmol/kg dry mass, respectively] and 2 but not 4 wk after CrS. An apparent placebo main effect of increased peak power and cumulative work was found after placebo and CrS, but no treatment (CrS) main effect was found on either variable. Thus, despite the rise and washout of muscle TCr and CrP, maximal intermittent sprinting performance was unchanged by CrS. ergogenic aids; creatine washout; muscle performance; fatigue CREATINE SUPPLEMENTATION (CrS) in humans has been reported to elevate muscle total creatine content (TCr), as well as enhance maximal intermittent exercise performance (6, 15, 19). Demonstrated mechanisms for this performance enhancement include a reduced ATP degradation during maximal exercise, due to elevated muscle Cr phosphate (CrP) content, particularly in type II muscle fibers (6). In addition, an accelerated rate of CrP resynthesis has been reported in some individuals after CrP depletion induced by electrical stimulation (16) but not voluntary exercise (6, 33). Three studies have reported an ergogenic effect of CrS on maximal intermittent exercise performance, together with verification of an elevated muscle TCr or CrP (2, 6, 37). The first two studies employed an ordered, single-group, nonblinded experimental design. Therefore, it cannot be excluded that their reported performance enhancement resulted from a placebo effect (2, 6). Although an ergogenic effect was

European Journal of Applied Physiology, Aug 16, 2023

Perturbations in K + have long been considered a key factor in skeletal muscle fatigue. However, ... more Perturbations in K + have long been considered a key factor in skeletal muscle fatigue. However, the exercise-induced changes in K + intra-to-extracellular gradient is by itself insufficiently large to be a major cause for the force decrease during fatigue unless combined to other ion gradient changes such as for Na +. Whilst several studies described K +-induced force depression at high extracellular [K + ] ([K + ] e), others reported that small increases in [K + ] e induced potentiation during submaximal activation frequencies, a finding that has mostly been ignored. There is evidence for decreased Cl − ClC-1 channel activity at muscle activity onset, which may limit K +-induced force depression, and large increases in ClC-1 channel activity during metabolic stress that may enhance K + induced force depression. The ATP-sensitive K + channel (K ATP channel) is also activated during metabolic stress to lower sarcolemmal excitability. Taking into account all these findings, we propose a revised concept in which K + has two physiological roles: (1) K +-induced potentiation and (2) K +-induced force depression. During low-moderate intensity muscle contractions, the K +-induced force depression associated with increased [K + ] e is prevented by concomitant decreased ClC-1 channel activity, allowing K +-induced potentiation of sub-maximal tetanic contractions to dominate, thereby optimizing muscle performance. When ATP demand exceeds supply, creating metabolic stress, both K ATP and ClC-1 channels are activated. K ATP channels contribute to force reductions by lowering sarcolemmal generation of action potentials, whilst ClC-1 channel enhances the force-depressing effects of K + , thereby triggering fatigue. The ultimate function of these changes is to preserve the remaining ATP to prevent damaging ATP depletion.

Membrane excitability is a critical regulatory step in skeletal muscle contraction and is modulat... more Membrane excitability is a critical regulatory step in skeletal muscle contraction and is modulated by local ionic concentrations, conductances, ion transporter activities, temperature, and humoral factors. Intense fatiguing contractions induce cellular K ϩ efflux and Na ϩ and Cl Ϫ influx, causing pronounced perturbations in extracellular (interstitial) and intracellular K ϩ and Na ϩ concentrations. Muscle interstitial K ϩ concentration may increase 1-to 2-fold to 11-13 mM and intracellular K ϩ concentration fall by 1.3-to 1.7-fold; interstitial Na ϩ concentration may decline by 10 mM and intracellular Na ϩ concentration rise by 1.5-to 2.0-fold. Muscle Cl Ϫ concentration changes reported with muscle contractions are less consistent, with reports of both unchanged and increased intracellular Cl Ϫ concentrations, depending on contraction type and the muscles studied. When considered together, these ionic changes depolarize sarcolemmal and t-tubular membranes to depress tetanic force and are thus likely to contribute to fatigue. Interestingly, less severe local ionic changes can also augment subtetanic force, suggesting that they may potentiate muscle contractility early in exercise. Increased Na ϩ-K ϩ-ATPase activity during exercise stabilizes Na ϩ and K ϩ concentration gradients and membrane excitability and thus protects against fatigue. However, during intense contraction some Na ϩ-K ϩ pumps are inactivated and together with further ionic disturbances, likely precipitate muscle fatigue. potassium; sodium; Na ϩ-K ϩ-ATPase; exercise excitability MUSCLE CONTRACTION REQUIRES the propagation of action potentials (AP) along the sarcolemma and down the transversetubules where they activate voltage sensors and enable Ca 2ϩ release from the sarcoplasmic reticulum. Each AP comprises Na ϩ influx during the depolarization phase and K ϩ efflux for the repolarization phase. Cl Ϫ also diffuses into the sarcoplasm contributing to the repolarization phase because Cl Ϫ channels remain open during depolarization (9) and the Cl Ϫ equilibrium potential (E Cl) is near the resting membrane potential (E m) (23, 40). Thus it is unremarkable that intense muscle contractions also induce pronounced perturbations in muscle Na ϩ , K ϩ , and Cl Ϫ ions. The important question is whether these changes are linked to fatigue. Muscle fatigue can be defined as a transient and recoverable decline in muscle force and/or power with repeated or continuous muscle contractions. Although the mechanisms of muscle fatigue have been studied extensively, considerable debate and

European Journal of Applied Physiology, 2022

The cardiac T-wave peak-to-end interval (Tpe) is thought to reflect dispersion in ventricular rep... more The cardiac T-wave peak-to-end interval (Tpe) is thought to reflect dispersion in ventricular repolarisation, with abnormalities in Tpe associated with increased risk of arrhythmia. Extracellular K + modulates cardiac repolarisation and since arterial plasma K + concentration ([K + ]) rapidly increases during and declines following exercise, we investigated the relationship between [K + ] and Tpe with exercise. Methods Serial ECGs (Tpe, Tpe/QT ratio) and [K + ] were obtained from 8 healthy, normokalaemic volunteers and 22 patients with end-stage renal disease (ESRD), at rest, during and after exhaustive exercise. Results Post-exercise [K + ] nadir was 3.1 ±0.1, 5.0 ±0.2 and 4.0 ±0.1 mmol.L-1 (mean ± SEM) for healthy participants and ESRD patients before and after HD, respectively. In healthy participants, compared to pre-exercise, recovery-induced low [K + ] was associated with a prolongation of Tpe (110 ±8 vs. 87 ±5 ms, respectively, p=0.03) and an increase in Tpe/QT ratio (0.28 ±0.01 vs. 0.23 ±0.01, respectively, p=0.01). Analyses of serial data revealed [K + ] as a predictor of Tpe in healthy participants (β =-0.54 ±0.11, p=0.0007), in ESRD patients (β =-0.72 ±0.1, p < 0.0001) and for all data pooled (β =-0.64 ±0.52, p = 0.0007). The [K + ] was also a predictor of Tpe/QT ratio in healthy participants and ESRD patients. Conclusions Tpe and Tpe/QT ratio are predicted by [K + ] during exercise. Low [K + ] during recovery from exercise was associated with increased Tpe and Tpe/QT, indicating accentuated dispersion of ventricular repolarisation. The findings suggest that variations in [K + ] with physical exertion may unmask electrophysiological vulnerabilities to arrhythmia.

The Journal of Physiology, 2012

Key points Reactive oxygen‐based molecules generated within muscle fibres in both exercise and p... more Key points Reactive oxygen‐based molecules generated within muscle fibres in both exercise and pathological conditions can greatly affect muscle function. These and consequent reactions can lead to either decreased or increased force response by the contractile proteins, but the mechanisms are unknown. This study demonstrates that the increase in force response appears to be due to a specific chemical process, known as S‐glutathionylation, of a particular cysteine residue present on the troponin I molecule in fast‐twitch muscle fibres, which is involved in sensing and responding to changes in intracellular calcium levels. S‐Glutathionylation can occur when glutathione, the primary cellular anti‐oxidant, reacts with oxidized cysteine residues. S‐Glutathionylation of troponin I not only helps protect the molecule from oxidative stress, but evidently also makes the contractile apparatus much more sensitive to calcium ions. This process seemingly occurs in exercising humans and is like...

Journal of Applied Physiology, Nov 1, 2016

Dissociation between short-term unloading and resistance training effects on skeletal muscle Na ϩ... more Dissociation between short-term unloading and resistance training effects on skeletal muscle Na ϩ ,K ϩ-ATPase, muscle function, and fatigue in humans.

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Journal of applied physiology (Bethesda, Md. : 1985), Jan 10, 2018

Effects of regular use of cold-water immersion (CWI) on fiber type-specific adaptations in muscle... more Effects of regular use of cold-water immersion (CWI) on fiber type-specific adaptations in muscle K transport proteins to intense training, along with their relationship to changes in mRNA levels after the first training session, were investigated in humans. Nineteen recreationally-active men (24{plus minus}6 y, 79.5{plus minus}10.8 kg, 44.6{plus minus}5.8 mL∙kg∙min) completed six weeks of sprint-interval cycling either without (passive rest; CON) or with training sessions followed by CWI (15 min at 10{degree sign}C; COLD). Muscle biopsies were obtained before and after training to determine abundance of Na,K-ATPase isoforms (α, β) and FXYD1, and after recovery treatments (+0h and +3h) on the first day of training to measure mRNA content. Training increased (p<0.05) the abundance of α and β in both fiber types, β in type-II fibers, and decreased FXYD1 in type-I fibers, whereas α and α abundance was not altered by training (p>0.05). CWI after each session did not influence resp...

Journal of applied physiology (Bethesda, Md. : 1985), May 10, 2018

Intense exercise induces pronounced hyperkalemia, followed by transient hypokalemia in recovery. ... more Intense exercise induces pronounced hyperkalemia, followed by transient hypokalemia in recovery. We investigated whether the β-agonist salbutamol attenuated the exercise-hyperkalemia, and exacerbated the post-exercise hypokalemia, and whether hypokalemia was associated with impaired cardiac repolarization (QT hysteresis). Eleven healthy adults participated in a randomized, counterbalanced, double-blind trial receiving either 1000 µg salbutamol (SAL) or placebo (PLAC) by inhalation. Arterial plasma potassium concentration ([K]) was measured at rest, during 3 min intense rowing exercise and 60 min recovery. QT hysteresis was calculated from ECG (n=8). [K] increased above baseline during exercise (rest, 3.72{plus minus}0.7 vs end-exercise, 6.81{plus minus}1.4 mM, P<0.001, mean{plus minus}SD) and decreased rapidly during early recovery to below baseline; restoration was incomplete at 60 min post-exercise (P<0.05). [K] was less during SAL than PLAC (4.39{plus minus}0.13 vs. 4.73{pl...

Little is understood about the fibre type-dependent regulation of Na+,K+-ATPase (NKA) isoforms by... more Little is understood about the fibre type-dependent regulation of Na+,K+-ATPase (NKA) isoforms by exercise training in humans. The main aim of this study was therefore to assess the impact of a period of repeated exercise sessions on NKA-isoform protein abundance in different skeletal muscle fibre types in men. Post-exercise cold-water immersion (CWI) has been reported to increase oxidative stress, which may be one mechanism underlying increases in NKA-isoform expression. Thus, a second aim was to evaluate the effect of CWI on training-induced modulation of NKA-isoform abundance. Vastus lateralis muscle biopsies were obtained from nineteen men at rest before (Pre) and after (Post) six weeks of intense interval cycling, with training sessions followed by passive rest (CON, n=7) or CWI (10 degrees C; COLD, n=5). Training increased (p<0.05) the abundance of NKAa1 and NKAb3 in both type I and type II fibres, NKAb1 in type II fibres, but was without effect on NKAa2 and NKAa3 (p>0.0...

We investigated the effect of a session of sprint-interval exercise on the mRNA content of NKA is... more We investigated the effect of a session of sprint-interval exercise on the mRNA content of NKA isoforms (α1-3, β1-3) and FXYD1 in human skeletal muscle. To explore some of the cellular stressors involved in this regulation, we evaluated the association between these mRNA responses and those of the transcription factors Sp1, Sp3 and HIF-1α. Given cold exposure perturbs muscle redox homeostasis, which may be one mechanism important for increases in NKA-isoform mRNA, we also explored the effect of post-exercise cold-water immersion (CWI) on the mRNA responses. Muscle was sampled from nineteen men before (Pre) and after (+0h, +3h) exercise plus passive rest (CON, n=10) or CWI (10°C; COLD, n=9). In COLD, exercise increased NKAα2and Sp1 mRNA (+0h, p<0.05). These genes remained unchanged in CON (p>0.05). In both conditions, exercise increased NKAα1, NKAβ3and HIF-1α mRNA (+3h; p <0.05), decreased NKAβ2mRNA (+3h; p<0.05), whereas NKAα3, NKAβ1, FXYD1 and Sp3 mRNA remained unchange...

Journal of applied physiology (Bethesda, Md. : 1985), Jan 22, 2015

The Na(+), K(+)-ATPase (NKA) plays a key role in muscle excitability, but little is known in huma... more The Na(+), K(+)-ATPase (NKA) plays a key role in muscle excitability, but little is known in human skeletal muscle about fiber-type specific differences in NKA isoform expression or adaptability. A vastus lateralis muscle biopsy was taken in 17 healthy young adults to contrast NKA isoform protein relative abundance between type I and IIa fibers. We further investigated muscle fiber-type specific NKA adaptability in 8 of these adults following four weeks repeated-sprint exercise (RSE) training, comprising three sets of 5x4-s sprints, three days/week. Single fibers were separated and myosin heavy chain (MHC-I, MHC-IIa) and NKA (α1-3 and β1-3) isoform abundance were determined via western blotting. All six NKA isoforms were expressed in both type I and IIa fibers. No differences between fiber types were found for α1, α2, α3, β1 or β3 isoform abundances. The NKA β2 isoform was 27% more abundant in type IIa than type I fibers (p<0.05), with no other fiber-type specific trends evident....

Springer eBooks, 2003

The present study investigated whether there were any differences between males and females in re... more The present study investigated whether there were any differences between males and females in respect to creatine transporter (CreaT) gene expression and/or total creatine (TCr) content in human vastus lateralis muscle. Skeletal muscle obtained from young healthy male (n = 13, age: 23.2 +/- 5.0 years) and female subjects (n = 12, age: 21.7 +/- 4.3 years) was analyzed for CreaT mRNA, CreaT protein and TCr content. Total CreaT protein content in the muscle was similar (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05) between the sexes. Two bands (approximately 55 and 73 kDa) of the CreaT protein were detected in all muscle samples. Both the 55 and the 73 kDa bands were present in similar (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05) amounts in males compared with females. The 73 kDa band was in greater abundance (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) than the 55 kDa band, irrespective of gender. In addition, CreaT mRNA expression relative to beta-actin mRNA and the TCr content (males: 117.8 +/- 2.2, females: 125.3 +/- 4.3 mmol.kg(-1) dry mass) were also unaffected (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05) by gender. These data demonstrate that gender does not influence skeletal muscle TCr content and CreaT gene expression in young human subjects.

Kidney International, 2003

Impaired K ؉ regulation contributes to exercise limitation in ing incremental exercise testing, r... more Impaired K ؉ regulation contributes to exercise limitation in ing incremental exercise testing, reaching only 50 to 60% end-stage renal failure. of healthy control levels [reviewed in 1]. It is likely that Background. Patients with end-stage renal failure (ESRF) impairments in muscle O 2 delivery, due to anemia [2-4], exhibit grossly impaired maximal exercise performance. This depressed muscle blood flow [5] and capillary rarefaction study investigated whether K ϩ regulation during exercise is [6], contribute to the depressed V O 2 peak during exercise impaired in ESRF and whether this is related to reduced exercise performance. in ESRF. However, improvements in V O 2 peak with Methods. Nine stable hemodialysis patients and eight conepoetin (EPO) are considerably less than expected from trols (CON) performed incremental cycling exercise to voliincreases in hemoglobin concentration ([Hb]) [1, 2, 5], tional fatigue, with measurement of peak oxygen consumption while normalization of [Hb] to 14 g • dL Ϫ1 with EPO in (V O 2 peak). Arterial blood was sampled during and following ESRF does not restore normal V O 2 peak values [7]. In exercise and analyzed for plasma [K ϩ ] (P K). Results. The V O 2 peak was approximately 44% less in ESRF addition, muscle mitochondrial O 2 utilization probably than in CON (P Ͻ 0.001), whereas peak exercise P K was greater is reduced also, as indicated by abnormalities in mito-(7.23 Ϯ 0.38 vs. 6.23 Ϯ 0.14 mmol • L Ϫ1 , respectively, P Ͻ 0.001). chondrial structure [8] and impaired post-contractile In ESRF, the rate of rise in P K during exercise was twofold metabolic recovery [6]. Thus, numerous factors in the greater (0.43 Ϯ 0.05 vs. 0.23 Ϯ 0.03 mmol • L Ϫ1 •min Ϫ1 , P Ͻ oxygen transport and utilization chain may limit exercise 0.005) and the ratio of rise in P K relative to work performed performance in ESRF, but additional factors are also was 3.7-fold higher (90.1 Ϯ 13.5 vs. 24.7 Ϯ 3.3 nmol • L Ϫ1 • J Ϫ1 , P Ͻ 0.001). A strong inverse relationship was found between important. V O 2 peak and the ⌬P K • work Ϫ1 ratio (r ϭ Ϫ0.80, N ϭ 17, P Ͻ Muscle fatigue is consistently reported as a major or 0.001). sole subjective factor causing exercise termination in Conclusions. Patients with ESRF exhibit grossly impaired ESRF [7, 9]. The mechanisms of fatigue are multifactoextrarenal K ϩ regulation during exercise, demonstrated by an rial, but include disturbances in muscle sodium ([Na ϩ ])

Journal of Sports Sciences, Mar 1, 1989

Nine male triathletes were studied during 160 min of exercise at 65% VO2 max on two occasions to ... more Nine male triathletes were studied during 160 min of exercise at 65% VO2 max on two occasions to examine the effect of glucose polymer ingestion on energy and fluid balance. During one trial they received 200 ml of a 10% glucose polymer solution at 20 min intervals during exercise (CHO), while in the other they received an equal volume of a sweet placebo (CON). On average, blood glucose levels (CON = 4.2 +/- 0.2 mmol l-1, CHO = 4.8 +/- 0.1, mean +/- S.E.) and respiratory exchange ratios (CON = 0.84 +/- 0.01, CHO = 0.87 +/- 0.01) during exercise were higher (P less than 0.05) as a result of the glucose polymer ingestion. There were no differences between trials, however, in the estimated plasma volume changes during exercise. Exercise time to exhaustion at an intensity corresponding to 110% VO2 max, performed 5 min after the submaximal exercise, was not influenced by glucose polymer ingestion. Relative to a control exercise bout conducted without prior exercise, however, sprint performance and postexercise blood lactate accumulation were impaired in both trials. It is concluded that glucose polymer ingestion maintains blood glucose levels and a high rate of carbohydrate oxidation during prolonged exercise, without compromising fluid balance.

Journal of Applied Physiology, May 1, 1998

Six men were studied during four 30-s ''all-out'' exercise bouts on an air-braked cycle ergometer... more Six men were studied during four 30-s ''all-out'' exercise bouts on an air-braked cycle ergometer. The first three exercise bouts were separated by 4 min of passive recovery; after the third bout, subjects rested for 4 min, exercised for 30 min at 30-35% peak O 2 consumption, and rested for a further 60 min before completing the fourth exercise bout. Peak power and total work were reduced (P Ͻ 0.05) during bout 3 [765 Ϯ 60 (SE) W; 15.8 Ϯ 1.0 kJ] compared with bout 1 (1,168 Ϯ 55 W, 23.8 Ϯ 1.2 kJ), but no difference in exercise performance was observed between bouts 1 and 4 (1,094 Ϯ 64 W, 23.2 Ϯ 1.4 kJ). Before bout 3, muscle ATP, creatine phosphate (CP), glycogen, pH, and sarcoplasmic reticulum (SR) Ca 2ϩ uptake were reduced, while muscle lactate and inosine 5Ј-monophosphate were increased. Muscle ATP and glycogen before bout 4 remained lower than values before bout 1 (P Ͻ 0.05), but there were no differences in muscle inosine 5Ј-monophosphate, lactate, pH, and SR Ca 2ϩ uptake. Muscle CP levels before bout 4 had increased above resting levels. Consistent with the decline in muscle ATP were increases in hypoxanthine and inosine before bouts 3 and 4. The decline in exercise performance does not appear to be related to a reduction in muscle glycogen. Instead, it may be caused by reduced CP availability, increased H ϩ concentration, impairment in SR function, or some other fatigue-inducing agent.