We have blocked creatine kinase (CK)-mediated phosphocreatine (PCr) -->/<-- ATP transphosphorylation in skeletal muscle by combining targeted mutations in the genes encoding mitochondrial and cytosolic CK in mice. Contrary to expectation, the PCr level was only marginally affected, but the compound was rendered metabolically inert. Mutant muscles in vivo showed significantly impaired tetanic force output, increased relaxation times, altered mitochondrial volume and location, and conspicuous tubular aggregates of sarcoplasmic reticulum membranes, as seen in myopathies with electrolyte disturbances. In depolarized myotubes cultured in vitro, CK absence influenced both the release and sequestration of Ca2+. Our data point to a direct link between the CK-PCr system and Ca2+-flux regulation during the excitation and relaxation phases of muscle contraction.

We investigated the capacity for torque development and muscle activation at the onset of fast voluntary isometric knee extensions at 30, 60, and 90 degrees knee angle. Experiments were performed in subjects (n = 7) who had high levels (>90%) of activation at the plateau of maximal voluntary contractions. During maximal electrical nerve stimulation (8 pulses at 300 Hz), the maximal rate of torque development (MRTD) and torque time integral over the first 40 ms (TTI40) changed in proportion with torque at the different knee angles (highest values at 60 degrees ). At each knee angle, voluntary MRTD and stimulated MRTD were similar (P < 0.05), but time to voluntary MRTD was significantly longer. Voluntary TTI40 was independent (P > 0.05) of knee angle and on average (all subjects and angles) only 40% of stimulated TTI40. However, among subjects, the averaged (across knee angles) values ranged from 10.3 +/- 3.1 to 83.3 +/- 3.2% and were positively related (r2 = 0.75, P < 0.05) to the knee-extensor surface EMG at the start of torque development. It was concluded that, although all subjects had high levels of voluntary activation at the plateau of maximal voluntary contraction, among subjects and independent of knee angle, the capacity for fast muscle activation varied substantially. Moreover, in all subjects, torque developed considerably faster during maximal electrical stimulation than during maximal voluntary effort. At different knee angles, stimulated MRTD and TTI40 changed in proportion with stimulated torque, but voluntary MRTD and TTI40 changed less than maximal voluntary torque.

An inverse relationship exists between striated muscle fiber size and its oxidative capacity. This relationship implies that muscle fibers, which are triggered to simultaneously increase their mass/strength (hypertrophy) and fatigue resistance (oxidative capacity), increase these properties (strength or fatigue resistance) to a lesser extent compared to fibers increasing either of these alone. Muscle fiber size and oxidative capacity are determined by the balance between myofibrillar protein synthesis, mitochondrial biosynthesis and degradation. New experimental data and an inventory of critical stimuli and state of activation of the signaling pathways involved in regulating contractile and metabolic protein turnover reveal: (1) higher capacity for protein synthesis in high compared to low oxidative fibers; (2) competition between signaling pathways for synthesis of myofibrillar proteins and proteins associated with oxidative metabolism; i.e., increased mitochondrial biogenesis via AMP-activated protein kinase attenuates the rate of protein synthesis; (3) relatively higher expression levels of E3-ligases and proteasome-mediated protein degradation in high oxidative fibers. These observations could explain the fiber type–fiber size paradox that despite the high capacity for protein synthesis in high oxidative fibers, these fibers remain relatively small. However, it remains challenging to understand the mechanisms by which contractile activity, mechanical loading, cellular energy status and cellular oxygen tension affect regulation of fiber size. Therefore, one needs to know the relative contribution of the signaling pathways to protein turnover in high and low oxidative fibers. The outcome and ideas presented are relevant to optimizing treatment and training in the fields of sports, cardiology, oncology, pulmonology and rehabilitation medicine.Electronic supplementary materialThe online version of this article (doi:10.1007/s00421-010-1545-0) contains supplementary material, which is available to authorized users.

Selected contractile properties and fatigability of the quadriceps muscle were studied in seven spinal cord–injured (SCI) and 13 able‐bodied control (control) individuals. The SCI muscles demonstrated faster rates of contraction and relaxation than did control muscles and extremely large force oscillation amplitudes in the 10‐Hz signal (65 ± 22% in SCI versus 23 ± 8% in controls). In addition, force loss and slowing of relaxation following repeated fatiguing contractions were greater in SCI compared with controls. The faster contractile properties and greater fatigability of the SCI muscles are in agreement with a characteristic predominance of fast glycolytic muscle fibers. Unexpectedly, the SCI muscles exhibited a force–frequency relationship shifted to the left, most likely as the result of relatively large twitch amplitudes. The results indicate that the contractile properties of large human locomotory muscles can be characterized using the approach described and that the transformation to faster properties consequent upon changes in contractile protein expression following SCI can be assessed. These measurements may be useful to optimize stimulation characteristics for functional electrical stimulation and to monitor training effects induced by electrical stimulation during rehabilitation of paralyzed muscles. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 1249–1256, 1999.

The effects of single isovelocity shortening contractions on force production of the electrically stimulated human adductor pollicis muscle were investigated in seven healthy male subjects. Redeveloped isometric force immediately following isovelocity shortening was always depressed compared with the isometric force recorded at the same muscle length but without preceding shortening. The maximal isometric force deficit (FD) was (mean ± s.e.m.) 37 ± 2 % after 38 deg of shortening at 6.1 deg s−1. The FD was positively correlated with angular displacement (r2 > 0.98) and decreased with increasing velocity of the shortening step. Stimulation at 20 Hz instead of 50 Hz reduced absolute force levels during the contractions to about 73 % and the FD was decreased to a similar extent. Eighty‐nine per cent of the velocity‐related variation in the FD could be explained by the absolute force levels during shortening. FD was largely abolished by allowing the muscle to relax briefly (approximately 200 ms), a time probably too short for significant metabolic recovery. At all but the highest velocities there was a linear decline in force during the latter part of the isovelocity shortening phase, suggesting that the mechanisms underlying FD were active during shortening. Our results show that shortening‐induced force deficit is a significant feature of human muscle working in situ and is proportional to the work done by the muscle‐tendon complex. This finding has important implications for experimental studies of force‐velocity relationships in the intact human.

1. We have examined the force-velocity characteristics of tetanically activated human adductor pollicis working in vivo, in the fresh and fatigued states. 2. The increase in force in response to stretch was divided into two major components. The first, steady, component persisted after the stretch and is concluded not to be a function of active cycling cross-bridges because it was not affected by either the velocity of the stretch or the level of muscle activation. 3. The origin of the second, transient, component of the increased force seen during stretch is consistent with cross-bridge activity since it increased with increasing velocity of stretch and was proportional to the level of activation. 4. It is likely that both components of the stretch response make a significant contribution to muscle performance when acting to resist a force. For the fastest stretch used, the contributions of cross-bridge and non-cross-bridge mechanisms were equal. For the slowest stretch, lasting 10 s and over the same distance, the force response was attributed almost entirely to non-cross-bridge mechanisms. 5. As a result of acute fatigue (50% isometric force loss) there were only small reductions in the non-cross-bridge component of the force response to stretch, while the cross-bridge component decreased in absolute terms. 6. The transient component of the stretch response increased as a result of fatigue, relative to the isometric force, while the force during shortening decreased. The results are consistent with a decrease in cross-bridge turnover in fatigued muscle. Keywords:

Whole-Body vibration (WBV) may lead to muscle contractions via reflex activation of the primary muscle spindle (Ia) fibres. WBV has been reported to increase muscle power in the short term by improved muscle activation. The present study set out to investigate the acute effects of a standard WBV training session on voluntary activation during maximal isometric force production (MVC) and maximal rate of force rise (MRFR) of the knee extensors. Twelve students underwent a single standard WBV training session: 5x1 min vibration (frequency 30 Hz, amplitude 8 mm) with 2 min rest in between. During vibration, subjects stood barefoot on the vibration platform with their knees at an angle of 110 degrees. At 90 s following vibration, maximal voluntary knee extensor force was reduced to 93 (5)% [mean (SD), P<0.05] of baseline value and recovered within the next 3 h. Voluntary activation remained significantly depressed (2-4%). Neither the electrically induced MRFR nor voluntary MRFR were significantly affected by WBV. In addition, six WBV training sessions in 2 weeks ( n=10) did not enhance either voluntary muscle activation during MVC [99 (2)% of the baseline value] or voluntary MRFR [98 (9)% of the baseline value]. It is concluded that in the short term, WBV training does not improve muscle activation during maximal isometric knee extensor force production and maximal rate of force rise in healthy untrained students.

To explore the cause of higher skeletal muscle fatigue resistance in women than men, we used electrically evoked contractions (1 s on, 1 s off, 30 Hz, 2 min), which circumvent motivational bias and allow examination of contractile properties. We compared 29 men [26.5 (7.0) years old; mean (S.D.)] with 35 women [25.4 (7.6) years old]. Strength of the quadriceps muscle was higher in men than women (P < 0.001). The lower maximal rate of relaxation in women (P = 0.002) indicates that their muscles were slower than those of men. The torque declined less in women than in men [37.7 (10.7) versus 29.9 (10.0)%; P = 0.002], and was not related to muscle strength or size, as determined with magnetic resonance imaging. The sex difference in fatigability was also seen when the circulation to the leg was occluded [torque declined 76.9 (10.8) versus 59.5 (16.9)% in men versus women, respectively; P = 0.008]. The maximal rate of relaxation correlated with the fatigability of the muscle under all conditions (correlations ranging from 0.34 to 0.51, P < 0.02). We conclude that the sex-related difference in skeletal muscle fatigue resistance is not explicable by differences in motivation, muscle size, oxidative capacity and/or blood flow between sexes, but might be related to differences in fibre type composition.