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Kinetics of morphine-sensitive [3H]-acetylcholine release from the guinea-pig myenteric plexus.

1 Longitudinal muscle-myenteric plexus preparations from the guinea-pig ileum were superfused at a constant rate while isotonic contractions were monitored. 2 The preparations were superfused with [3H]-choline while stimulated supramaximally at 0.1 Hz followed by washout in the presence of hemicholinium-3. The evoked release of the label due to a second 0.1 Hz stimulation in the absence of an anticholinesterase was measured. 3 Evoked efflux of the label was initially fast followed by a slower phase. 4 Morphine reduced the size of the pool and the rate of the initial fast efflux and the size of the pool but not the rate of the slow efflux evoked by supramaximal stimulation. 5 Submaximal stimulation reduced only the size of the pools from which the fast and slow efflux originated. 6 Naloxone reversed the depression of contractions and evoked release produced by morphine. 7 Results suggest that 0.1 Hz stimulation releases [3H]-acetylcholine simultaneous from two pools. The fast release may originate from spontaneously firing units whose rate of discharge is depressed by morphine, while the slow release originates from neurones which do not fire spontaneously and whose threshold to field stimulation is increased by morphine.

Acetylcholine↗

The effect of gallamine, gallopamil and nifedipine on responses to acetylcholine and carbachol in the taenia of the guinea-pig caecum.

The effects of gallamine, gallopamil and nifedipine on isotonic contractions of the isolated taenia of the guinea-pig caecum produced by acetylcholine (ACh) or carbachol (CCh) were investigated. Gallamine (0.1 to 0.3 mM) inhibited contractions produced by CCh more than those produced by ACh. The difference was still present after pretreatment of the tissue with paraoxon (10 microM for 20 min) to inhibit cholinesterases or in experiments carried out in the presence of tetrodotoxin (0.3 microM) to exclude possible ganglionic stimulation by the agonists. Gallopamil or nifedipine selectively inhibited the tonic response to ACh in the absence or presence of paraoxon. The phasic response to ACh or the tonic response to CCh (0.1 or 1 microM) was much less affected. Reduction of the Ca2+ content of the bath medium reduced phasic and tonic responses to ACh more than the tonic response to CCh. These results suggest that there are differences in the interaction of ACh and CCh with muscarinic receptors in this muscle.

Acetylcholine↗

Contractile responses to substance P and related peptides of the isolated muscularis mucosae of the guinea-pig oesophagus.

The site of action of substance P and related tachykinins with respect to isotonic contractions was examined on the isolated muscularis mucosae attached to the submucous plexus of the guinea-pig oesophagus. Substance P (greater than 30 nM) produced a concentration-dependent contraction of the muscularis mucosae (EC50 1.9 +/- 0.5 microM, n = 10). The contractions were rapid in onset (2 min or less), sustained, reversible by washing and the preparation did not show tachyphylaxis. Eledoisin and physalaemin produced similar sustained contraction of the muscularis mucosae. The order of sensitivity was eledoisin greater than substance P greater than physalaemin. Contractions induced by 1 microM of each tachykinin were not significantly modified by incubation of the tissue with substance P or eledoisin (10 microM for 30 min). The contractile responses to tachykinins were unaffected by tetrodotoxin (0.3 microM), atropine (0.3 microM), phentolamine (1 microM), chlorpheniramine (1 microM), methysergide (1 microM), baclofen (100 microM) and verapamil (10 microM), but were abolished by the incubation of the tissue with calcium-free, EGTA (0.1 mM)-containing Tyrode solution. A substance P antagonist, [D-Pro2, D-Trp7,9]-substance P (greater than 0.1 microM), produced a transient contraction of the muscularis mucosae and the smooth muscle regained its original tone within 6 to 10 min. Contractions to the tachykinins were now inhibited by the antagonist (0.1-10 microM) in a concentration-dependent manner, the order of sensitivity being physalaemin greater than substance P = eledoisin. The cholinergically mediated electrically (0.1 Hz, 0.5 ms, supramaximal voltage)-induced twitch contractions of the muscularis mucosae were not significantly modified by substance P (0.01-0.3 microM). 7 The present results indicate that substance P and related tachykinins contract the isolated muscularis mucosae of the guinea-pig oesophagus by a direct action on the smooth muscle, probably by stimulating SP-E receptors.

Animals↗

Analysis of variation in L-365,260 competition curves in radioligand binding assays.

1. For several years, we have used the cholecystokinin (CCK)B/gastrin receptor selective antagonist, L-365,260, as a reference compound in a variety of studies in CCKB/gastrin receptor radioligand binding assays. Here, we have analysed the competition curve data sets obtained between L-365,260 and [125I]-BH-CCK8S in guinea-pig gastric gland and mouse and rat cerebral cortex preparations. 2. Competition curves obtained for L-365,260 in the mouse cortex assay were not different from rectangular hyperbolae (slope = 1.01 +/- 0.02) implying the presence of a single population of binding sites (pKI = 8.41 +/- 0.01; data from 47 experiments, slope constrained to unity). However, in the rat cortex and guinea-pig gastric gland assays, the mean slope of the competition curves was significantly less than one and the mean apparent pKI significantly lower than that obtained in the mouse cortex (slope = 0.85 +/- 0.03, 0.90 +/- 0.03; apparent pKI = 7.98 +/- 0.05, 8.07 +/- 0.05; 48 and 45 experiments, in rat and guinea-pig, respectively). The distribution of the individual pKI and slope estimates of the competition curves in these two assays was consistent with expectations for the variable expression (in terms of absolute number and proportion) of two binding sites. The two sites were characterized by pKI values for L-365,260 of 8.50 +/- 0.04 and 8.48 +/- 0.04 for the high affinity site and 7.32 +/- 0.04 and 7.22 +/- 0.06 for the low affinity site in guinea-pig and rat, respectively. 3. The affinity estimates for L-365,260, although obtained on different tissues, are consistent with data obtained from the analysis of L-365,260 antagonism of pentagastrin-stimulated responses in mouse and rat stomach (acid secretion) and guinea-pig gastric muscle (isotonic contraction) assays. To this extent, these data suggest the existence of two CCKB/gastrin receptor subtypes.

Animals↗

AT1 receptors mediate angiotensin II-induced release of nitric oxide in afferent arterioles.

BACKGROUND: Recent studies have indicated that angiotensin II (Ang II) possibly activates the nitric oxide (NO) system. We investigated the role of AT receptor subtypes (AT-R) in mediating the Ang II-induced NO release in afferent arterioles (Af) of mice. METHODS: Isolated Af of mice were perfused, and the isotonic contraction measured. Further, NO release was determined using DAF-FM, a fluorescence indicator for NO. Moreover, we qualitatively assessed the expression of AT-R at the mRNA level using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Ang II reduced luminal diameters dose dependently (67.3 +/- 6.3% at 10(-6) mol/L). Inhibition of AT2-R with PD123.319 did not change the Ang II contractile response. AT1-R blockade with ZD7155 inhibited contraction. Stimulation of AT2-R during AT1-R inhibition with ZD7155, and preconstriction with norepinephrine (NE) had no influence on the diameter. Drug application via the perfusion pipette changed flow and pressure, and enhanced NO fluorescence by DeltaF = 4.0 +/- 0.4% (N= 14, background). Luminal application of Ang II (10(-7) mol/L) increased the NO fluorescence by DeltaF = 9.9 +/- 1.2% (N= 8). AT1-R blockade blunted the increase to background levels (DeltaF to 4.0 +/- 0.3%, N= 6, P < 0.05), but AT2-R blockade did not (8.1 +/- 0.9%, N= 9). L-NAME nearly abolished the Ang II effect on the NO fluorescence (DeltaF = 1.6 +/- 0.5% (N= 8). NE did not increase NO release beyond the background levels. RT-PCR showed expression of both AT1-R and AT2-R. CONCLUSION: The results indicate an Ang II-induced NO release in Af of mice, which is mediated by AT1-R. Thus, Ang II balances its own constrictor action in Af. This control mechanism is very important in view of high renin and angiotensin II concentration in the juxtaglomerular apparatus.

Angiotensin II↗

A comparison of hand-held isometric strength measurement with isokinetic muscle strength measurement in the elderly.

OBJECTIVE: To compare hand-held isometric muscle strength measurement to an isokinetic muscle strength measurement in a healthy elderly population. DESIGN: Cross-sectional survey. SETTING: Retirement community in Southeastern Arizona. PARTICIPANTS: Thirty-two volunteers (16 men and 16 women) age 60 and over (mean age 70.3 years) who were free of musculoskeletal problems and did not have significant health problems. INTERVENTIONS: None. MEASUREMENTS: Isometric muscle strength was determined using a hand-held isometric strength device (Penny and Giles) for elbow flexion and extension and knee flexion and extension. Isokinetic muscle strength (average peak torque and average work per repetition) was measured on the same individuals using a Lido isokinetic dynamometer. RESULTS: Correlations between the strength measurement techniques were generally favorable with the lowest correlation being .72, (95 percent confidence interval .50-.86) and the highest being .85, (95 percent confidence interval .72-.93). However, there was substantial variability of hand-held strength reading at some levels of isokinetic strength. CONCLUSIONS: Hand-held dynamometry for strength measurement correlates strongly with measurement of strength using isokinetic dynamometry. Despite these high correlations, there is remaining variability of hand-held muscle strength readings when compared with isokinetic strength measurement at some levels of isokinetic muscle strength. Modification of the testing methodology or instrumentation used in this study is needed to improve the consistency of these measurements.

Aged↗

Regional differences in the contractile and intracellular Ca2+ responses of the guinea-pig vas deferens to neurotransmitters and excess K+.

The contractile responses to various concentrations of noradrenaline (NA), adenosine triphosphate (ATP), acetylcholine (ACh) and excess external K+ in the epididymal, middle and prostatic portions of the guinea-pig vas deferens were investigated by measuring the isotonic contraction, and the intracellular Ca2+ concentration ([Ca2+]i) using fura-2 fluorescence. In the epididymal portion, the contractions evoked by each of these agonists were biphasic, comprising a transient followed by a tonic phase. In the middle portion, NA and ACh evoked biphasic contractions, whereas the ATP-induced contraction was an almost monophasic transient. In contrast, in the prostatic portion, only transient contractions were evoked by ACh and ATP, while the NA-induced contraction was oscillatory. The responses to each of the neurotransmitters in the three portions were not affected by pretreatment with TTX. The maximal responses of tonic contraction in response to each of the neurotransmitters were largest in the epididymal portion, decreased in the middle and were almost absent in the prostatic portion. These regional differences in the contractile properties of the vas deferens were also evident upon stimulation with excess external K+. As with the contractile responses, regional differences in the [Ca2+]i increases were observed during exposure to all the stimulants. It is suggested that the regional differences in the contractile responses of the vas deferens to various neurotransmitters and excess external K+ may involve variation in the mechanisms of Ca2+ homeostasis and in the sensitivity of the contractile apparatus to intracellular Ca2+ ions.

Acetylcholine↗

Sodium dependence of the inward spread of activation in isolated twitch muscle fibres of the frog.

1. The excitatory process travelling along the T-system may be either electrotonic or regenerative. If Na(+) dependent action potential is present in the tubular membranes, high frequency of stimulation might cause a Na(+) depletion in the tubules sufficient to abolish this process.2. We tested this hypothesis by recording tension in isolated muscle fibres stimulated tetanically (up to 60 shocks/sec). In low [Na(+)] solutions, output tension was initially similar to that in normal Ringer, but then fell smoothly to a substantially lower value.3. The activity of individual myofibrils was recorded directly with ciné-micrographs during isotonic contractions while the fibres were stimulated at high frequencies. In low [Na(+)](o) wavy myofibrils appeared in the centre of the fibre and spread towards the periphery, indicating failure of activation. Wavy myofibrils never appeared in normal Ringer.4. Intracellular action potentials recorded during the tetanic stimulation indicated that the inactivated myofibrils present in low [Na(+)] solutions cannot be explained by the changes in size and duration of the action potential.5. Our results strongly suggest the existence of a regenerative Na(+) conductance in the tubular membrane during the inward spread of an excitatory process.

Action Potentials↗

Dynamic properties of denervated fast and slow twitch muscle of the cat.

1. Isometric and isotonic contractions were recorded from cat flexor digitorum longus (FDL) and soleus muscles denervated for 28-35 days and compared with the responses of contralateral control muscles.2. Isometric twitch time to peak was longer in the denervated muscles than in the controls. Tetanic tension was reduced whether expressed as absolute units, per gram or per unit area. Absolute twitch tensions were reduced less below the control values with a consequent increase of twitch-tetanus ratio. These results agree with earlier reports; but, in contrast, there was no reduction in the relative rate of rise of tension in the isometric tetanus of denervated compared with control FDL. The maximum rate of rise of tension in the twitch was only a little less than that in the fully fused tetanus in the denervated muscles.3. Whole muscle shortening velocity was reduced in the denervated soleus with no change in the number of sarcomeres per fibre. There was a smaller change in FDL muscles. This was the result of an increase in the number of sarcomeres per fibre which followed denervation in FDL, compensating for a decreased velocity of shortening of the sarcomere. Maximum sarcomere shortening velocity was reduced by 30% relative to control values in both muscles.4. Measurements were made of the isometric contractions resulting from pairs of stimuli in an attempt to assess the period of maximal activation in the twitch. Maximum summation occurred when the second stimulus was given close to the time of the peak of the twitch in the denervated muscles.

Animals↗

Filament sliding and energy absorbed by the cross-bridge in active muscle subjected to cycical length changes.

1. The effects of single and double cycles of stretch and release on the tension response and relative sliding movement of the actin and myosin filaments in active frog's muscle were investigated. 2. The cross-bridges linking the filaments together are able to accommodate a greater range of filament displacement before becoming detached during a second cycle stretch, providing it commences without delay following the preceding release: sarcomere 'give' then occurs for displacements of around 18 nm, as compared with 12 nm for a first cycle stretch. It is postulated that the difference arises because the myosin heads adopt different 'preferred' positions in the isometric steady-state and at the end of a previous release. 3. Muscle length-tension loops were recorded and used to measure the energy absorbed when a muscle is subjected to cycles of stretch and release. The work absorbed per unit length change increases with increasing displacement of the cross-bridges from their initial (isometric) steady-state position, up to the point at which sarcomere 'give' occurs (S2); thereafter it remains constant. 4. More work is absorbed during the first cycle of a double stretch-release combination than during the second. The greater amount absorbed during the first cycle is associated with a correspondingly greater amount of filament sliding in the period following sarcomere 'give'. Sarcomere length-tension loops were constructed and these showed that not less than 80-85% of the work done on a muscle is absorbed by the sarcomeres themselves. 5. A greater amount of work is done on stretching up to (but not beyond) S2 during second cycle stretch as compared to a first. The difference amounts about 1 mJ.m-2 per half-sarcomere. 6. The results are compatible with the mechanism for force production proposed by Huxley & Simmons (1973), in which each myosin head generates force in a number of stepping movements, from one attached state to another. It is concluded that (a) during an unloaded isotonic contraction the working 'stroke' of the head would result in a 10-13 nm relative sliding movement of the filaments, and (b) the potential energy difference separating the two 'preferred' states is 6-9.6 kT per cross-bridge, or 3-4.8 kT per S-1 sub-units, assuming that each one interacts simultaneously with the actin filament.

Actins↗

Reduced effect of pH on skinned rabbit psoas muscle mechanics at high temperatures: implications for fatigue.

1. Inhibition of actomyosin function by decreased pH has been proposed to account for much of the depression of muscle function during fatigue. The clearest support for this hypothesis has been from studies of skinned skeletal muscle fibre mechanics at low temperatures (< or = 15 degrees C). 2. We re-examined the effect of decreased pH (7.0-6.2) on skinned mammalian skeletal fibre mechanics at low (10 degrees C) and high (30 degrees C) temperatures, using recently developed protocols that allow reproducible mechanical data to be obtained at higher temperatures. 3. At 10 degrees C we duplicated previous observations of a significant inhibition of maximum shortening velocity (Vmax) and isometric tension (Po) by acidosis. In contrast, at the higher temperature, we found only a very minimal effect of acidosis on Vmax and a threefold reduction in the decrease in Po. 4. Thus at temperatures only slightly below physiological for mammalian skeletal muscle systems, pH plays a much less important role in the process of muscle fatigue at the cross-bridge level than has been suggested by data obtained at physiologically unrealistic temperatures.

Acidosis↗

alpha 1-adrenoceptor-mediated negative inotropy of adrenaline in rat myocardium.

1. The effect of alpha- and beta-adrenoceptor stimulation on isotonic contraction was investigated on right ventricular papillary muscles of the rat, stimulated at a rate of 0.5 Hz. 2. Adrenaline (0.5 microM) induced a slight but significant negative inotropic effect: shortening decreased from 0.137 +/- 0.058 to 0.122 +/- 0.059 muscle lengths (mean +/- S.D.; -11%, P < 0.0001) and maximum shortening velocity from 2.9 +/- 1.2 to 2.7 +/- 1.3 muscle lengths s-1 (-7%, P < 0.025). 3. The negative inotropic effect of adrenaline was enhanced after blocking the beta-adrenoceptors with 50 microM atenolol. On the other hand, exposure to adrenaline after blocking the alpha-adrenoceptors with 50 microM phentolamine resulted in an increase in shortening as well as in maximum shortening velocity. 4. Stimulation of the beta-adrenoceptors with 0.5 microM isoprenaline caused marked positive inotropic effects, whereas stimulation of the alpha 1-adrenoceptors with 0.5 microM phenylephrine regularly resulted in a long-lasting decrease in shortening and maximum shortening velocity. 5. 1,2-Dioctanoyl-sn-glycerol (1,2-DOG) and adrenaline induced an activation of protein kinase C (PKC) with translocation of this enzyme from the cytosol to the sarcolemma. 6. Activation of PKC with 10 microM 1,2-DOG and 0.5 microM adrenaline was accompanied by a decrease in shortening and maximum shortening velocity. Inhibition of PKC with 0.1 microM staurosporine abolished the negative inotropic effect of adrenaline. 7. From these results we conclude that a low dose of adrenaline stimulates not only beta-but also alpha-adrenoceptors and that the observed negative inotropic effect of adrenaline is mediated by alpha 1-adrenoceptors, linked to the diacylglycerol-PKC signal transduction pathway.

Animals↗

Predictions of mechanical output of the human M. triceps surae on the basis of electromyographic signals: the role of stimulation dynamics.

In order to assess the significance of the dynamics of neural control signals for the rise time of muscle moment, simulations of isometric and dynamic plantar flexion contractions were performed using electromyographic signals (EMG signals) of m. triceps surae as input. When excitation dynamics of the muscle model was optimized for an M-wave of the medial head of m. gastrocnemius (GM), the model was able to make reasonable predictions of the rise time of muscle moment during voluntary isometric plantar flexion contractions on the basis of voluntary GM EMG signals. The rise time of muscle moment in the model was for the greater part determined by the amplitude of the first EMG burst. For dynamic jumplike movements of the ankle joint, however, no relationship between rise time of muscle moment in the experiment and muscle moment predicted by the model on the basis of GM EMG signals was found. Since rise time of muscle moment varied over a small range for this movement, it cannot be completely excluded that stimulation dynamics plays a role in control of these simple single-joint movements.

Adult↗

Models of contractile units and their assembly in smooth muscle.

It is believed that the contractile filaments in smooth muscle are organized into arrays of contractile units (similar to the sarcomeric structure in striated muscle), and that such an organization is crucial for transforming the mechanical activities of actomyosin interaction into cell shortening and force generation. Details of the filament organization, however, are still poorly understood. Several models of contractile filament architecture are discussed here. To account for the linear relationship observed between the force generated by a smooth muscle and the muscle length at the plateau of an isotonic contraction, a model of contractile unit is proposed. The model consists of 2 dense bodies with actin (thin) filaments attached, and a myosin (thick) filament lying between the parallel thin filaments. In addition, the thick filament is assumed to span the whole contractile unit length, from dense body to dense body, so that when the contractile unit shortens, the amount of overlap between the thick and thin filaments (i.e., the distance between the dense bodies) decreases in exact proportion to the amount of shortening. Assembly of the contractile units into functional contractile apparatus is assumed to involve a group of cells that form a mechanical syncytium. The contractile apparatus is assumed malleable in that the number of contractile units in series and in parallel can be altered to accommodate strains on the muscle and to maintain the muscle's optimal mechanical function.

Actins↗

Force-velocity constants in smooth muscle: afterloaded isotonic and quick-release methods.

In using pharmacologic stimuli, force-velocity (FV) curves are usually obtained by the method of quick release (QR) and redevelopment of shortening at peak tetanic tension; the advantage of the method being that the active state is at maximum. However, the QR may itself reduce the intensity of the active state and result in reduced values of FV constants. We tested this by delineating FV curves in canine tracheal smooth muscle using both conventional afterloaded isotonic contractions (ALI), and redevelopment of shortening after QR methods. For both these studies a supramaximal tetanizing electrical stimulus was used. The analysis of 11 experiments revealed that the latter method resulted in statistically significant reductions of all FV constants except for Po (maximum isometric tetanic tension). The means and standard errors for the sets of constants for the ALI and QR, respectively, are as follows: Vmax (maximum velocity of shortening) = 0.275 lo (optimal muscle length)/s +/- 0.024 (SE), and 0.216 lo/s + 0.023; a (hyperbolic constant with units of force) = 294 g/cm2 +/- 35 and 236 g/cm2 +/- 32; b (hyperbolic constant with units of velocity) = 0.059 lo +/- 0.004 and 0.039 lo/s +/- 0.005; a/Po = 0.214 +/- 0.028 and 0.182 +/- 0.026; and Po = 1.362 kg/cm2 +/- 0.106 and 1.294 kg/cm2 +/- 0.097. These data clearly show that the quick-release method for measuring force-velocity relationships in canine smooth muscle results in significant underestimates of muscle shortening properties.

Animals↗

Human group I excitatory projections from ankle dorsiflexors to quadriceps muscle.

A short latency projection of group I afferent fibers from ankle dorsiflexors to knee extensor muscles has been categorized as species specific to humans. However, the effects of the pathway have only been inferred from conditioning homonymous reflexes in relaxed muscle. This study focused directly on the responses evoked in the electromyogram of the heteronymous muscles when active, in two experiments. In the first, preferential activation of group I afferents of ankle dorsiflexors, by electrical stimulation of the common peroneal nerve, excited both vastus medialis (mean latency, 26.3 ms) and rectus femoris (mean latency, 33.5 ms). No excitation or inhibition in either muscle was associated with stimulation of the tibial nerve. The second experiment compared vastus medialis responses with common peroneal nerve stimulation during three different movement conditions in which the muscle was equally contracted: rhythmic isotonic (pedalling); episodic isotonic; isometric contraction. Responses were identified in all three active states, with no significant differences in amplitude or latency. No responses were seen in the relaxed muscle.

Adult↗

Cross-bridge kinetics and shortening in smooth muscle.

Stiffness measurements were performed on smooth muscle preparations from guinea-pig taenia coli to obtain information on the number of attached cross bridges under varying contractile conditions. The normalized stiffness of the cross-bridge system in smooth muscle may be of a magnitude similar to that assumed in skeletal muscle. Transition from isometric contraction to unloaded shortening was associated with a decrease in stiffness to 50% or less of the isometric value, slightly higher than that found in skeletal muscle fibers. Comparison of phasic (5 s) and tonic (5 min) contractions showed lower Vmax, intracellular [Ca2+], and myosin 20 kDa light chain phosphorylation at 5 min, indicating development of a latch state. Isometric force and stiffness were identical in the two types of contraction. However, stiffness during unloaded shortening was greater in the latch state, which may be the result of the presence of a population of cross bridges with a low rate constant for detachment.

Animals↗

Auxotonic loading and airway smooth muscle shortening.

Isometric and isotonic contractions represent two extremes in loading regimens that can be imposed on a contracting smooth muscle preparation in vitro. Under physiological conditions, however, it is likely that smooth muscle in hollow organs contracts against auxotonic loads, the magnitude of which is a function of muscle shortening. Therefore, attempts to determine physiologically significant contractile properties of smooth muscle should be made under auxotonic loading conditions. An electronic loader was built to provide four auxotonic loading modes: linear, logarithmic, sigmoidal, and exponential. These shortening-dependent auxotonic loads were imposed on an actively shortening canine tracheal smooth muscle. Results confirmed that (i) active force generated by the muscle is load dependent but that (ii) at the same load borne by the muscle in its steady state, i.e., at the same maximum force generated by the muscle, the maximum shortenings under different loading modes were significantly altered. The shortening was maximal under the exponential loading mode, which provided the smallest load in the early phase of contraction, while it was the least under the logarithmic loading mode, which provided the greatest load in that phase. We concluded that the shortening achieved by an airway smooth muscle was a function not only of the magnitude of the final load imposed on the muscle but, more importantly, of the time course of loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗