Isometric Twitch Force Research Articles

A decrease in soleus muscle force generation in rats after downhill running.

The purpose of the present study was to investigate the immediate and 48-hr post-exercise effects of eccentric contraction-biased exercise on the contractile properties of the soleus muscle in situ. Adult male Wistar rats were categorised into sedentary control rats (n = 10), rats studied immediately (n = 10), and rats studied 48 hours after the exercise (n = 10). The exercise protocol consisted of a 90-min intermittent downhill running (-16 degrees, 16 m/min) on a motor-driven treadmill. The contractile properties of the soleus muscle were recorded following i.p. chloral hydrate anaesthesia. Isometric twitch force (Pt), time-to-peak tension (TPT), half-relaxation time (1/2 RT), and tetanic force at stimulation frequencies of 40, 80, and 100 Hz were recorded. A low-frequency muscle fatigue protocol (stimulation at 4 Hz for 5 min) was applied to test for fatigability. The main findings indicated that Pt generation dropped both immediately and 48 hr after the exercise, while tetanic force was partially restored after 48 hr. Exercise-induced E-C coupling failure and contractile machinery disorganisation due to muscle injury are put forward as the main force reduction causes.

Force reduction uncoupled from pH and H(2)PO(-)(4) in rat gastrocnemius in vivo with continuous 2-Hz stimulation.

The aim of this study was to examine the effect of the products of ATP hydrolysis on the fatigue process in rat gastrocnemius in vivo. Adult male Sprague-Dawley rats (300-400 g) were anesthetized and ventilated in a custom-built cradle fitted with a force transducer that could be placed into a 7-T NMR magnet. The muscle was stimulated continuously at 2 Hz for 20 min (n = 7). Isometric twitch force increased in the first 4 min of stimulation accompanied by changes in twitch duration (20% increase in relaxation time). Prolonged relaxation was associated with changes in cytosolic pH (6.91 to 6.58), lactate (1.8 to 12.6 micromol/g wet wt), and H(2)PO (7.57 to 13.99 mM). After 4 min, relaxation time, pH, lactate, and H(2)PO returned toward control values as twitch force progressively decreased. No correlation was found between force decline (or twitch broadening) and total phosphate (3 to 23 mM), free [ADP] (18 to 95 microM), free [Mg(2+)] (0.58 to 0.96 mM), or free energy of ATP hydrolysis (-65 to -55 kJ/mol). We conclude that force decline is not due to increased pH and/or H(2)PO but to fatigue of the fast-twitch fibers, possibly linked to glycogen depletion and/or failure of nerve impulse transmission in these fibers.

Influence of mild hypothermia on myocardial contractility and circulatory function.

Myocardial contractility depends on temperature. We investigated the influence of mild hypothermia (37-31 degrees C) on isometric twitch force, sarcoplasmic reticulum (SR) Ca2+-content and intracellular Ca2+-transients in ventricular muscle strips from human and porcine myocardium, and on in vivo hemodynamic parameters in pigs. In vitro experiments: muscle strips from 5 nonfailing human and 8 pig hearts. Electrical stimulation (1 Hz), simultaneous recording of isometric force and rapid cooling contractures (RCCs) as an indicator of SR Ca2+-content, or intracellular Ca2+-transients (aequorin method). In vivo experiments: 8 pigs were monitored with Millar-Tip (left ventricle) and Swan-Ganz catheter (pulmonary artery). Hemodynamic parameters were assessed at baseline conditions (37 degrees C), and after stepwise cooling on cardiopulmonary bypass to 35, 33 and 31 degrees C. Hypothermia increased isometric twitch force significantly by 91 +/- 16 % in human and by 50 +/- 9 % in pig myocardium (31 vs. 37 degrees C; p < 0.05, respectively). RCCs or aequorin light emission did not change significantly. In anesthetized pigs, mild hypothermia resulted in an increase in hemodynamic parameters of myocardial contractility. While heart rate decreased from 111 +/- 3 to 73 +/- 1 min(-1), cardiac output increased from 2.4 +/- 0.1 to 3.1 +/- 0.31/min, and stroke volume increased from 21 +/- 1 to 41 +/- 3 ml. +dP/dtmax increased by 25 +/- 8% (37 vs. 31 degrees C; p < 0.05 for all values). Systemic and pulmonary vascular resistance did not change significantly during cooling. Mild hypothermia exerts significant positive inotropic effects in human and porcine myocardium without increasing intracellular Ca2+-transients or SR Ca2+-content. These effects translate into improved hemodynamic parameters of left ventricular function.

Effects on dystrophic ( dy/dy) limb muscle of the K + channel blocker tetraethylammonium

K + channel blockers, such as tetraethylammonium (TEA) and 4-aminopyridine, increase force of normal skeletal muscle. To determine whether they also increase force of diseased muscle, effects of TEA were examined on limb muscles of dy/dy dystrophic mice in vitro. TEA significantly increased isometric twitch force of normal and dystrophic soleus muscle by 29.9±5.8 and 30.0±5.0%, respectively, and significantly increased force of normal and dystrophic extensor digitorum longus muscle by 18.3±1.9 and 34.9±10.4%, respectively. Force increases could be attributed only partially to a prolongation of contraction time. These data indicate that TEA augments force of overtly diseased (dystrophic) limb muscle to an extent comparable with that of normal limb muscle.

Hybrid logistic characterization of isometric twitch force curve of isolated ferret right ventricular papillary muscle.

We previously found that the isovolumic pressure curve of the left ventricle and the isometric twitch force curve of the right ventricular in situ papillary muscle, both of the blood-perfused canine heart, were precisely fitted by our newly proposed hybrid logistic function. This function describes the difference between the two S-shaped logistic functions for the rising and falling components: A/[1+exp{-(4B/A)(t-C)}]-D/[1+exp{-(4E/D)(t-F)}]+G. This function characterizes comprehensively both ventricular and in situ papillary muscle contraction and relaxation. In the present study, we hypothesized that this function could also characterize the force curve of the most popular, standard-type, isolated and Tyrode-superfused papillary muscle preparation. To test this hypothesis, we investigated how precisely the hybrid logistic function could fit 112 isometric twitch force curves observed in eight isolated and Tyrode-superfused ferret right ventricular papillary muscles at different muscle lengths and extracellular Ca2+ concentrations. We always obtained a precise curve fitting with a correlation coefficient above 0.9987. This fitting was much more precise than sinusoidal and polynomial exponential function curve fittings. These results supported the present hypothesis. We conclude that our hybrid logistic function reasonably characterizes the force curve of the isolated myocardial preparation. This result broadens the generality of the hybrid logistic characterization of ventricular isovolumic pressure and myocardial isometric twitch force generation. The hybrid logistic characterization seems to be an integrative expression of contractile processes in myocardial twitch contraction.

Electrophysiologic and inotropic effects of K+-channel blockade in aged diaphragm.

The aminopyridines block several types of potassium (K+) channels and exert a direct inotropic effect on skeletal muscle by prolonging the duration of the action potential. Aging influences skeletal muscle Cl- channels and their regulation, and affects both resting whole-cell K+ conductance and adenosine triphosphate (ATP)-sensitive K+ channels, although in opposite directions. The present study tested the hypothesis that aging affects diaphragm-muscle K+ channels responsible for repolarization of the action potential and force production. Diaphragms of young adult (age 3 to 4 mo) and old (age 20 to 21 mo) male Fischer 344 rats was studied in vitro at 37 degrees C. The K+-channel blocker 3,4-diaminopyridine (DAP, 0.3 mM) did not alter resting membrane potential or action-potential height, overshoot, or rate of depolarization of either young-adult or old muscle. However, DAP slowed the rate of repolarization of the action potential and increased the action-potential area in young-adult and old muscle; the time for the action potential to repolarize by 80% increased from 0.59 +/- 0.02 ms (mean +/- SE) to 3.37 +/- 0.68 ms (p < 0.05) in young-adult muscle and from 0.87 +/- 0.06 ms to 2.52 +/- 0.54 ms (p < 0.05) in old muscle, whereas the action-potential area increased from 56 +/- 3 mVms to 193 +/- 34 mVms (p < 0.05) in young-adult muscle and from 72 +/- 5 mVms to 134 +/- 20 mVms (p < 0. 05) in old muscle. The action-potential area was not different in young-adult and old diaphragm without DAP, but was significantly larger in young-adult than in old diaphragm with DAP (p < 0.05). The functional consequence was that DAP increased diaphragm isometric twitch force by 181 +/- 12% (p < 0.05) in young-adult muscle and by 144 +/- 24% (p < 0.05) in old muscle; the increase was significantly greater in young-adult than in old muscle (p < 0.05). These data suggest an aging-associated reduction in, or reduced DAP sensitivity of, diaphragm K+ conductance during action potentials, which most likely reflects aging-associated alterations in delayed-rectifier K+ conductance. Although the inotropic effect of DAP was greater for young-adult than for old diaphragm muscle, the difference was sufficiently modest to show that DAP has substantial inotropic effects in old muscle.

Salbutamol enhances isotonic contractile properties of rat diaphragm muscle.

The effects of the beta2-adrenoceptor agonist salbutamol (Slb) on isometric and isotonic contractile properties of the rat diaphragm muscle (Diamus) were examined. A loading dose of 25 microg/kg Slb was administered intracardially before Diamus excision to ensure adequate diffusion. Studies were then performed with 0.05 microM Slb in the in vitro tissue chamber. cAMP levels were determined by radioimmunoassay. Compared with controls (Ctl), cAMP levels were elevated after Slb treatment. In Slb-treated rats, isometric twitch and maximum tetanic force were increased by approximately 40 and approximately 20%, respectively. Maximum shortening velocity increased by approximately 15% after Slb treatment, and maximum power output increased by approximately 25%. During repeated isotonic activation, the rate of fatigue was faster in the Slb-treated Diamus, but both Slb-treated and Ctl Diamus fatigued to the same maximum power output. Still, endurance time during repetitive isotonic contractions was approximately 10% shorter in the Slb-treated Diamus. These results are consistent with the hypothesis that beta-adrenoceptor stimulation by Slb enhances Diamus contractility and that these effects of Slb are likely mediated, at least in part, by elevated cAMP.

CELLULAR DIVERSITY DOES NOT CONFOUND MECHANICAL AND ENERGETICS MEASUREMENTS

1333 Cellular heterogeneity could potentially invalidate conclusions drawn at the intracellular and molecular level from functional and biochemical studies of muscle made at a macroscopic level. We measured the size of such effects by quantifying the mechanical and energetic properties of anterior compartment muscles of the lower leg to graded electrical stimulation of the anterior tibial nerve in normal subjects. Maximal nerve stimulation, documented by surface EMG and isometric twitch force, activates all motorneurones. Lower intensity, which is thought to excite only the more excitable population of“fast” motorneurons, gave a reduced EMG and twitch force. We measured the ATPase rate from the initial decline in PCr content during 90 sec of steady state twitches at 100% and 30% of maximal force and the ATP synthesis rate from the rate of return of PCr to control levels. The ATPase rate was proportional to the force developed (at maximal and 0.3 max.), i.e. the economy (ATPase per tension-time integral) was the same. However the economy differed among individuals. Max. or submax. stimulation did not affect the time constant for ATP synthesis or the rise and fall times of the twitch; these properties also differed among individuals. Thus nerve stimulation which selects for fast-twitch motorneurones vs. the entire muscle made no difference in the bioenergetic and mechanical characteristics in an individual. We conclude 1. non-invasive bioenergetic and mechanical methods show in a specific muscle that cellular characteristics vary in different individuals, 2. cellular diversity does not confound the interpretation of macroscopic results at the cellular level. The last conclusion may not apply to voluntary contractions.

Mechanism of action of endothelin in rat cardiac muscle: cross‐bridge kinetics and myosin light chain phosphorylation

1. The molecular mechanism of inotropic action of endothelin was investigated in rat ventricular muscle by studying its effects on characteristics of isometric twitch, barium-induced steady contracture and the level of incorporation of 32Pi into myosin light chain 2. 2. Exposure of rat papillary muscle to endothelin caused an increase in isometric twitch force but did not alter the twitch-time parameters. 3. Endothelin did not significantly change the maximum contracture tension but did cause an increase in contracture tension at submaximal levels of activation, without changes in the tension-to-stiffness ratio and kinetics of attached cross-bridges. Kinetics of attached cross-bridges were deduced during steady contracture from complex-stiffness values, and in particular from the frequency at which muscle stiffness assumes a minimum value, fmin. Endothelin did not alter fmin. 4. Endothelin caused an increase in the level of incorporation of 32Pi into myosin light chain 2 without a concurrent change in the level of incorporation of 32Pi into troponin I. 5. We conclude that the inotropic action of endothelin is not due to an increase in the kinetics of attached cross-bridges, nor due to a change in the force per unit cross-bridge, but may result from an increased divalent cation sensitivity caused by elevated myosin light chain 2 phosphorylation, resembling post-tetanic potentiation in fast skeletal muscle fibres.

Contractile Properties of Obliquely Striated Muscle from the Mantle of Squid (Alloteuthis Subulata) and Cuttlefish (Sepia Officinalis)

The mechanical properties of obliquely striated muscle fibres were investigated using thin slices of mantle from squid Alloteuthis subulata and cuttlefish Sepia officinalis. Brief tetani or twitch stimuli were used as this pattern is likely to occur during jetting of the intact animal. The length&shy;active force relationship for twitches and tetani (0.1s, 50Hz) was similar to that of vertebrate cross-striated fibres. Passive force at the length giving maximum tetanic force was 0.13&plusmn;0.05P0 (mean &plusmn; s.e.m., N=6, where P0 is maximum isometric tetanus force) and increased steeply at longer lengths. Peak force in a brief isometric tetanus (0.2s, 100&shy;150Hz) was 262&plusmn;16mNmm-2 cross-sectional area of wet tissue (N=6) for squid, and 226&plusmn;19mNmm-2 (N=7) for cuttlefish. The force&shy;velocity relationship for isotonic shortening during twitches of squid mantle slices was a 'double hyperbolic' relationship as described for cross-striated fibres by Edman. Fitting Edman's equation to the results gave: P*=1.18&plusmn;0.07, Vmax=2.43&plusmn;0.11Ltws-1 and 1/G=0.69&plusmn;0.13 (N=8), where P* is the intercept on the force axis expressed relative to Ptw, peak isometric twitch force, Vmax is the intercept on the velocity axis, Ltw is the length at which Ptw is produced and G is the constant expressing curvature. The large values of 1/G indicate that the force&shy;velocity relationship is not very curved. Maximum power was produced during shortening at 0.45&plusmn;0.03Ptw (N=8). Maximum power during twitch contraction was 18.3&plusmn;1.7mWg-1wetmass or, expressed in relative units, (V/Vmax)(P/Ptw), where V is the velocity during shortening and P is the force during shortening, was 0.16&plusmn;0.01 (N=8), which is higher than that of many cross-striated locomotor muscles.

Late depression of muscle excitability in humans after fatiguing stimulation.

1. Changes in muscle excitation and in isometric twitch force have been studied for up to 8 h after fatiguing stimulation of the human biceps brachii. 2. Within 10 s of a cessation of the 20 Hz fatiguing tetanus, the amplitudes of the M waves (muscle compound action potentials) had returned to control values, whereas the twitch forces were reduced in all subjects. The M waves then decreased in amplitude over the next 3 h, reaching a mean value that was 42.4 +/- 18.6% of control levels (means +/- S.E.M.; P < 0.001). 3. By 8 h, the mean M wave amplitude had recovered to 93.8 +/- 33.3% of control levels, while the corresponding mean twitch force was 104.1 +/- 36.9%. 4. The cellular mechanism responsible for the depression of the M wave is presently unknown, but it is likely to be postsynaptic and may involve Na+ channels.

The relationship between the intracellular Ca2+ transient and the isometric twitch force in frog muscle fibres.

The calcium-sensitive fluorescent indicator fluo-3 was used to monitor the intracellular free calcium concentration ([Ca2+]i) during isometric twitches in twenty-nine single muscle fibres from the anterior tibialis muscle of Rana temporaria (sarcomere length, 2.2 microns; 2-4 degrees C). The transient change in [Ca2+]i in response to a single stimulus was very brief. The time to peak and the duration of the Ca2+ signal, measured at 50% of the peak amplitude, were 8.3 +/- 0.2 and 22.1 +/- 1.4 ms (mean +/- S.E.M., n = 29), respectively. The mean peak amplitude of the Ca2+ transient was 3.2 +/- 0.1 microM, ranging from 2.46 to 3.92 microM among the different fibres. The isometric force started to rise 2.5 ms before [Ca2+]i reached its maximum value. When peak twitch force was attained, [Ca2+]i had already declined to approximately 10% of its maximum value. The peak force produced during a twitch was closely related to the decay phase of the Ca2+ transient, a slower decay of [Ca2+]i being associated with a greater amplitude of the twitch. The amplitude and duration of the Ca2+ transient varied in a systematic way relative to one another in different fibres, in that a greater amplitude was associated with a more rapid decay of the Ca2+ transient. NO3- and Zn2+ added to the external medium greatly enhanced the peak twitch force without markedly affecting the amplitude of the Ca2+ transient. However, both agents delayed the decay of [Ca2+]i. It is concluded that the decay phase of the Ca2+ transient is a more important determinant of the mechanical response during an isometric twitch than is the peak amplitude of the transient.

Logistic character of myocardial twitch force curve: simulation.

We found that the isovolumic pressure-time curve of the canine left ventricle closely fitted the difference of two logistic function curves and that the isovolumic relaxation-pressure curve segment was more reliably characterized by a logistic time constant than by the conventional exponential time constant. We therefore hypothesized that the calcium (Ca) transient and the Ca-troponin (Tn) binding and crossbridge (CB) kinetics underlay the logistic character of the ventricular isovolumic pressure curve. We tested this hypothesis with a computer simulation of a simple Ca and CB kinetics model of myocardial isometric twitch force development. We assumed the instantaneous number of attached CBs that was theoretically given as the difference between the cumulative CB attachment and detachment curves. We radically changed the Ca transient, Ca-Tn binding, and CB kinetic parameters. We always found that both the cumulative CB attachment and detachment curves closely fitted logistic functions. The difference curve of these two best-fit logistic functions closely fitted the theoretical F curve with certain combinations of the Ca transient, the Ca-Tn binding, and the CB kinetic parameters. These results seem to support our hypothesis.

Simultaneous Assessment of Isometric Forces in Fast- and Slow-Twitch Muscles of Single Rat Hindlimbs in Situ

An apparatus, consisting of a pair of small strain gauge transducers, was designed for the simultaneous assessment of isometric contractile function in two muscles, composed of a predominance of either fast- or slow-twitch fibers, and within a single rat hindlimb in situ. This facilitates assessment of mechanical performance of two separate muscles under identical conditions. In anesthetized rats (N = 10), the voltages and frequencies required to produce isometric twitch and tetanic forces from the soleus (SOL) and extensor digitorum longus (EDL) muscles were determined. The apparatus was then used to demonstrate the simultaneous assessment of forces produced by the SOL and EDL from the same hindlimbs (n = 5) during 30 min of fatigue and 30 min of recovery. With this apparatus, data collected were comparable to published data. The apparatus can be used for the simultaneous assessment of isometric contractile function and fatigue in both a fast- and a slow-twitch muscle of a single rat hindlimb in situ.

Effects of theophylline on pharyngeal dilator and diaphragm muscle contractile properties.

Theophylline alleviates central and obstructive apneas of prematurity, and may improve adult obstructive sleep apnea. One mechanism of action appears to be a stimulatory effect on the motor output to upper airway dilator muscles. The purpose of the present study was to determine whether theophylline might have a second mechanism of action, namely that of improving the force and/or endurance of the pharyngeal dilator musculature. Rat sternohyoid muscle strips were studied in vitro and compared to diaphragm strips. The isometric twitch force and twitch kinetics of neither muscle were altered by theophylline (100 mg/l). Theophylline significantly slowed the rate at which the diaphragm fatigued during intermittent 40-Hz stimulation (p < 0.001). In contrast, theophylline produced no improvement in the fatigue resistance of the sternohyoid muscle. The degree of force potentiation during the early portion of the fatigue protocol was not altered by theophylline for either muscle. These results suggest that the mechanism by which theophylline improves obstructive apnea is unlikely to be due to a beneficial effect on pharyngeal dilator muscle force or endurance.

Comparison of twitch force and calcium handling in papillary muscles from right ventricular pressure overload hypertrophy in weanling and juvenile ferrets

The aim was to compare differences in peak twitch force occurring despite similar degrees of right ventricular hypertrophy in ferrets with pulmonary artery banding at either weanling or juvenile age. After inducing pressure overload hypertrophy by banding the pulmonary artery of weanling and juvenile age ferrets, mechanical function (that is, isometric twitch force and passive stiffness), intracellular [Ca2+] using the calcium indicator aequorin, markers of myocardial energy supply, and quantified connective tissue content were studied. It was previously found that there was a reduced peak isometric twitch force despite normal [Ca2+]i in juvenile banded ferrets age 10-12 weeks with right ventricular pressure overload hypertrophy (POHj). In the present study we report findings in banded weanling ferrets (POHw) age 7 weeks. POHw animals showed a similar degree of hypertrophy to that found in the POHj. However, there was a greater peak twitch force in hypertrophied muscles at higher [Ca2+]o. There was no difference in peak [Ca2+]i: -3.1(SEM 0.1) v -3.1(0.3) (log fractional luminescence) at 16 mM [Ca2+]o for control and POHw, respectively. Connective tissue content for control animals was 10(1)% versus 10(2)% in POHw. Despite a lack of quantitative change in connective tissue content or resting [Ca2+]i in POHw, passive stiffness in papillary muscles was increased. Retrospective analysis of tissue from POHj revealed a connective tissue content of 24(6.8)% (P << 0.001). Thus the decreased peak twitch force reported in POHj might in part be due to an increase in fibrous connective tissue. In this study, lactate dehydrogenase was significantly higher (38%) in POHw animals. In contradistinction, total creatine kinase activity and total creatine content were significantly less (22%) in hearts from POHj animals, indicating differences in myocyte remodelling despite similar degrees and durations of hypertrophy. Comparison of POHw and POHj showed that, when there is restructuring of the extracellular space in terms of increased fibrosis, there is also molecular remodelling in the myocyte, as demonstrated by a decrease in the creatine kinase system.

Changes in pharyngeal respiratory muscle force produced by K + channel blockade

The purpose of the present study was to determine whether the contractility of pharyngeal respiratory muscles can be augmented by altering membranous K + channel conductance. The effects on twitch force of two K + channel blockers, tetraethylammonium (TEA, 10 mM) and 4-aminopyridine (4-AP, 0.3 mM), were examined in vitro for sternohyoid and diaphragm muscle strips. Both agents augmented isometric twitch force of both muscles. In response to TEA twitch force of the sternohyoid muscle increased significantly more than that of the diaphragm (by 33 ± 7 vs. 9 ± 1%, P = 0.004), whereas with 4-AP the increase in twitch force of the sternohyoid muscle was comparable to that of the diaphragm (55 ± 15 vs. 64 ± 6%, P = 0.50). 4-AP shifted the force-frequency relationship of both muscles leftward but did not alter peak tetanic force, so that force with 4-AP exceeded that without drug at stimulation frequencies below 60 Hz. In contrast TEA reduced force at stimulation frequencies > 20 Hz. The isometric contraction times of both muscles was variably prolonged, more so with 4-AP (by 30 ± 15% for the sternohyoid and 32 ± 3% for the diaphragm) than with TEA (by 9 ± 2% for the sternohyoid and 5 ± 2% for the diaphragm). For the group of muscles and K + channel blockers, the degree of augmentation of twitch force correlated with the degree of prolongation of contraction time (r = 0.82, P < 0.001), consistent with blocking delayed rectifier K + channels as the mechanism of increasing muscle force.

Contractile properties of the human triceps surae muscle during simulated weightlessness

The effect of a 120-day period of bed rest on the mechanical properties of human triceps surae muscle was studied in a group of male volunteers (n = 6, mean age 38 years). The results shows that the contractile properties of skeletal muscle in response to disuse change considerably. Time to isometric peak tension of the triceps surae muscle increased from 120 (SEM 3.0)ms to 136 (SEM 2.9)ms (P < 0.01), half relaxation time from 92 (SEM 2.1)ms to 100 (SEM 1.6)ms (P < 0.05) and total contraction time from 440 (SEM 9.9)ms to 540 (SEM 18.7)ms (P < 0.001). Isometric twitch force (Ft) decreased by a mean of 36.7% (P < 0.05), maximal voluntary contraction (MVC) and maximal force (Fmax) by a mean of 45.5% and 33.7%, respectively (P < 0.05-0.01). The value Fmax:Ft ratio increased by 3.6% (nonsignificant). The difference between Fmax and MVC, expressed as a percentage of Fmax and referred to as force deficiency, has also been calculated. Force deficit increased by a mean of 60% (P < 0.001) after bed rest. Force-velocity properties of the triceps surae muscle calculated according to an absolute scale of voluntary and electrically evoked contraction development decreased considerably. The calculations of the same properties on a relative scale did not differ substantially from the initial physiological state. The results would suggest that muscle disuse is associated with both atrophy and a reduction in contractility in the development of Fmax and decreased central (motor) drive. The change in the triceps surae muscle contractile velocity properties may indicate changes in the kinetically active state in the muscles.

Taurine depletion and excitation-contraction coupling in rat myocardium.

Although the sulfur-containing amino acid taurine is found in high concentrations in mammalian myocardium, its involvement in function of the cardiac myocyte remains unclear. To examine the effects of taurine depletion on cardiac mechanical function, rats were treated in vivo with the taurine transport antagonist guanidinoethane sulfonate (GES). After 6 weeks of treatment, myocardial taurine concentrations were decreased to < 40% of control, with no change in tissue DNA content. Right ventricular trabeculas from taurine-depleted rats exhibited significant reductions (P < .05) in isometric twitch force (Ft) at all [Ca2+]o levels and systolic sarcomere lengths examined. Taurine-depleted trabeculas also exhibited increased passive compliance. A slight (P < .05) rightward shift in the Ft-[Ca2+]o relation suggested a decrease in the sensitivity of the taurine-depleted muscles to [Ca2+]o. No changes were observed in the force-interval relation, suggesting that the transsarcolemmal Ca(2+)-handling mechanisms remained unchanged. The fraction of Ca2+ recirculated through the sarcoplasmic reticulum, inferred from the decay of postextrasystolic potentiation, was also not different in the taurine-depleted muscles. When force was expressed relative to the rate of stimulation, length of rest periods, or postextrasystolic potentiation, virtually all curves were super-imposable for control and taurine-depleted muscles, suggesting that the deficit was not dependent on Ca2+ handling. Thus, we conclude that in taurine-depleted muscles the force-generating processes showed the same regulation as in control muscle. Furthermore, the substantial deficit in force development is consistent with a reduced population of force generators on the basis of three pieces of evidence.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the creatine analogue β-guanidinopropionic acid on skeletal muscles of mice deficient in muscle creatine kinase

To evaluate the effects of phosphocreatine (PCr) and creatine (Cr) depletion on skeletal muscles of mice deficient in muscle creatine kinase (M-CK), we have fed mutant mice a diet containing the creatine analogue β-guanidinopropionic acid (βGPA). After 8–10 weeks of feeding, accumulation of the creatine analogue in M-CK-deficient muscles was comparable to that observed in muscles of wild-type mice. Strikingly, and unlike wild types, mutants did not accumulate phosphorylated βGPA, indicating that MM-CK is the only muscle CK isoform which can phosphorylate βGPA. In M-CK-deficient muscles there was respective depletion of PCr, Cr and ATP levels to 31, 41 and 83% of normal. The average cross-sectional area of type 2B fibres in gastrocnemius muscles was very much reduced and was similar to type 1 and type 2A fibres which maintained their normal size. The maximal isometric twitch force developed by gastrocnemius-plantaris-soleus (GPS) muscle complexes of βGPA-treated mutants was reduced by about 30%, but these muscles showed an increased fatigue resistance during 1 and 5 Hz contraction. Mitochondrial enzyme activities in the upper hind limb musculature of null mutants were 20–35% increased by the βGPA diet. Altogether, these results provide evidence that certain functions of the creatine kinase/phosphocreatine (CK/PCr) system are not eliminated solely by the loss of M-CK.