Lateral rectus whole muscle and motor unit contractile measures with the extraocular muscles intact

Both extracellular and intracellular stimulation of single motoneurons were shown to be similarly effective and consistent in eliciting contractile responses in single lateral rectus muscle motor units. The whole muscle was activated by stimulating the sixth nerve in the brain stem. Both whole muscle and motor unit contractile characteristics, under isometric conditions, were found to remain consistent regardless of whether this extraocular muscle was detached or left attached to the globe. In addition, whole muscle twitch and maximum tetanic tension evoked by sixth nerve stimulation was significantly less than would be predicted by the linear summation of individual motor unit twitch and maximum tetanic tensions.     

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.     

Activation of two types of fibres in rat extraocular muscles

1. The contractile responses of the inferior rectus, one of the extraocular muscles of the rat, to a depolarization induced by an elevation of the potassium concentration in the external medium ([K]O) have been studied 'in vitro'. 2. The elevation of [K]O to 20 and 30 mM-K produced contractures that consisted of a sustained or tonic tension. When [K]O was increased to 50 mM or more a well-defined transient or phasic tension appeared before the tonic response. The increment of [K]O above 50 mM enhanced the phasic component and depressed the tonic tension. The maximal tonic tension, usually evoked by 50 mM-K, is about 50% of the tetanic tension, shows a gradual decline with time and lasts for hours. Control experiments performed in diaphragm showed that this muscle only responds with phasic tensions. 3. The difference in the repriming of the phasic and tonic responses when tensions were induced with salines containing low or normal [Cl] suggests that the muscle fibres responsible for the tonic tension are poorly permeable to Cl-. 4. The amplitude of the tonic tension was reduced by Ca deprivation and by an elevation of [Ca] in the saline to 10 mM. 5. It is concluded that in rat extraocular muscles, an increase in [K]O activates two types of muscle fibres: singly and multiply innervated. These appear to be functionally equivalent to the twitch and slow fibres of amphibian and avian muscle and would give rise to the phasic and tonic components of the contracture, respectively.     

N-acetylcysteine depresses contractile function and inhibits fatigue of diaphragm in vitro

We have previously shown that antioxidant enzymes (superoxide dismutase and catalase) depress contractility of unfatigued diaphragm fiber bundles and inhibit development of acute fatigue. In the present study, we tested for similar effects of N-acetyl-cysteine (NAC), a nonspecific antioxidant approved for clinical use. Diaphragms were excised from deeply anesthetized rats. Fiber bundles were removed, mounted isometrically at 37 degrees C, and stimulated directly using supramaximal current intensity. Studies of unfatigued muscle showed that 10 mM NAC reduced peak twitch stress (P < 0.0001), shortened time to peak twitch stress (P < 0.002), and shifted the stress-frequency curve down and to the right (P < 0.05). Fiber bundles incubated in 0.1-10 mM NAC exhibited a dose-dependent decrease in relative stresses developed during 30-Hz contraction (P < 0.0001) with no change in maximal tetanic (200 Hz) stress. NAC (10 mM) also inhibited acute fatigue. Throughout 10 min of intermittent contraction at 30-40 Hz, treated bundles developed higher stresses than time-matched control bundles (P < 0.0001). NAC concentrations > or = 30 mM were toxic, causing a prompt irreversible decrease in maximal tetanic stress (P < 0.0001). Because NAC effects mimic the effects of other antioxidant agents with different mechanisms of action, we conclude that exogenous antioxidants exert stereotypical effects on contractile function that differ between unfatigued and fatiguing muscle. Unlike antioxidant enzymes, however, NAC has been approved for clinical use and may be used in future studies of human muscle fatigue.     

Lengthening contraction and interpretations of active state tension in the isometric twitch response of skeletal muscle

The plateau of tetanic tension in a lengthening contraction of muscle at any given length is always greater than that in an isometric contraction at the same given length. To account for this excess of tension, it is suggested that the contractile machinery is "locked" in a strained condition that might make the muscle capable of bearing a greater tension in a lengthening contraction than it can develop in an isometric contraction. It is proposed that this strained condition also occurs in a lengthening contraction of the twitch response. If this proposal is valid it seems certain that the plateu of tension in the lengthening contraction of the twitch response cannot be equated with the plateau of tension in the isometric contraction of tetanus. The design of the original concept, that the plateau of active state tension in the lengthening contraction of the twitch is equal to the plateau of tension (Po) in the isometric contraction of tetanus, is based upon the assumption that the contractile component is neither lengthening nor shortening during both of these plateaus. This assumption is made without considering the possibility that the plateau in the lengthening contraction might be due to concurrent lengthening of series elastic elements and shortening of the contractile component. To account for the plateau of tension observed after quick lengthening in the early phase of twitch contraction indirect evidence is presented favoring the view that the quick lengthening during stretch is followed by slow lengthening and stress relaxation (decrease of tension) in series elastic elements and simultaneous shortening and increase of tension in the contractile component. When the original concept of active state tension in the twitch response is interpreted in the light of lengthening contraction, it is concluded that the labeled or implied Po for the plateau of the active state tension is unwarranted and confusing. It seems that the primary source of confusion is the assumption that the tension a muscle is capable of bearing in a lengthening contraction is equatable with the tension it can develop in an isometric contraction.     

Inhibition of Ca2+ release in rat atrophied gastrocnemius muscle

Contractile parameters of a twitch contraction and changes in these parameters during repetitive stimulation are modified by muscle atrophy induced by tetrodotoxin (TTX). These altered parameters included developed tension (DT), contraction time (tC), half-relaxation time (tR, 1/2), average rate of force development (DT tC-1) and peak rate of relaxation (DTdtmin-1). These modifications may be related to different Ca2+ concentration transients in the myoplasm during muscle stimulation. We have used dantrolene sodium (DS) in TTX-treated rat gastrocnemius muscle to test this hypothesis. In situ isometric contractile responses of rat gastrocnemius muscle during repetitive stimulation at 10 Hz were analysed before and after administration of DS. After DS administration, twitch amplitude, tC, tR, 1/2 and DT tC-1 decreased and DTdtmin-1 relative to DT increased in atrophied muscle. During repetitive stimulation, a progressive enhancement developed tension (staircase) was absent in atrophied muscle, but DT increased to 171 +/- 4%, presenting a staircase response after DS treatment. This potentiation was accompanied by an increase in DT tC-1 to 175.6 +/- 7%. Inhibition of Ca2+ release in atrophied muscle resulted in twitch contractile parameters and contractile responses to 10 Hz stimulation that were similar, in many respects, to those responses in control (non-atrophied) muscles.     

Time course study of the isometric contractile properties of mdx mouse striated muscles

The isometric twitch and tetanic contractions of three hindlimb muscles (soleus, plantaris, extensor digitorum longus) were recorded in situ in groups of mdx and C57BL/10 control mice at young, adult and old ages (3, 4, 6, 8, 13, 26, 39 and 52 weeks). Based on a two-way analysis of variance (age/phenotype) the mdx phenotype did not modify the absolute tension but was associated with a significant decrease in the tetanic tension normalized to muscle weight in all the muscles which became heavier. These results suggest that the contractile material in mdx is not so powerful as in controls. Moreover, significantly faster time to peak and half-relaxation time were observed in mdx soleus and plantaris. Comparison between these contraction characteristics and those of other experimental models suggests that the high percentage of regenerated fibres in mdx muscles could play a role in modifying contractile properties.     

Adaptations of rat lateral gastrocnemius motor units in response to voluntary running

This study investigated the effects of 12 wk of voluntary wheel running on motor units from rat lateral gastrocnemius. Motor units were isolated via ventral root splitting (L5) from active or sedentary rats and were classified into slow, fast-fatigue-resistant, and fast-fatigable (FF) units. An overall increase in mean motor unit tetanic tension (35%) was accompanied by a decrease in mean motor unit fatigue resistance (-10%). These adaptations were localized in the fast unit population but varied among fast motor unit subtypes. The overall increase in tetanic force was due primarily to increases in fast-fatigue-resistant units (300%), whereas changes in fatigue resistance (-43%) were confined to FF units. However, the changes seen with activity may have been partly obscured by classifying fast motor units based on fatigability, since a significant increase in tetanic force accompanied by a decreased twitch one-half relaxation time was apparent in units falling in the midrange of the tetanic force continuum and included a number of FF units. These data provide direct demonstration of nonuniform motor unit adaptations subsequent to increases in normal functional activity.     

Functional significance of upper and lower motor neuron impairment in amyotrophic lateral sclerosis

The objective of this study was to examine the contribution of lower motor neuron (LMN) and upper motor neuron (UMN) dysfunction to weakness and impaired motor control in 27 patients with amyotrophic lateral sclerosis (ALS). Isometric strength was measured by dorsiflexor maximum voluntary contraction force (MVC). LMN function was measured by tetanic force, twitch force, and the amplitude of the compound muscle action potential. UMN function was measured by the speed of rapid foot taps, the maximum rate of rise of voluntary force, and the central activation ratio [CAR = MVC/(MVC + superimposed tetanic force)]. The results suggest that (1) LMN loss appears to be the primary cause of progressive weakness in ALS; while (2) UMN impairment in ALS leads to slowing of contraction speed and rapid movements, and modest decreases in central activation; and (3) during 6 months of progression, LMN changes were greater than UMN changes.     

The effect of ischemic preconditioning on the recovery of skeletal muscle following tourniquet ischemia

It has been well documented that ischemic preconditioning limits ischemic-reperfusion injury in cardiac muscle, but the ability of ischemic preconditioning to limit skeletal muscle injury is less clear. Previous reports have emphasized the beneficial effects of ischemic preconditioning on skeletal muscle structure and capillary perfusion but have not evaluated muscle function. We investigated the morphologic and functional consequences of ischemic preconditioning, followed by a 2-hour period of tourniquet ischemia on muscles in the rat hindlimb. The 2-hour ischemia was imposed without preconditioning, or was preceded by three brief (10 minutes on/10 minutes off) preischemic conditioning intervals. We compared muscle morphology, isometric contractile function, and muscle fatigue properties in predominantly fast-twitch, tibialis anterior muscles 3 (n = 8) and 7 (n = 8) days after ischemia-reperfusion. Two hours of ischemia, followed by reperfusion, results in a 20 percent reduction of muscle mass (p < 0.05) and a 33 percent reduction in tetanic tension (p < 0.05) when compared with controls (n = 8) at 3 days. The same protocol, when preceded by ischemic preconditioning, results in similar decreases in muscle mass and contractile function. Neuromuscular transmission was also impaired in both ischemic groups 7 days after ischemia. Nerve-evoked maximum tetanic tension was 69 percent of the tension produced by direct muscle stimulation in the ischemia group and 65 percent of direct tension in the ischemic preconditioning/ischemia group. In summary, ischemic preconditioning, using the same protocol reported to be effective in limiting infarct size in porcine muscle, had no significant benefit in limiting injury or improving recovery in the ischemic rat tibialis anterior. The value of ischemic preconditioning in reducing imposed ischemic-reperfusion-induced functional deficits in skeletal muscle remains to be demonstrated.     

Alterations in the force-frequency relationship by tert-butylbenzohydroquinone, a putative SR Ca2+ pump inhibitor, in rabbit and rat ventricular muscle

1. The effects of 2,5 di-(tert-butyl)-1,4-benzohydroquinone (TBQ), a putative inhibitor of the sarcoplasmic reticulum (SR) Ca2+ pump, on twitch tension, time course and SR Ca2+ content have been studied at different stimulation frequencies (0.5-3 Hz) in isolated preparations from the rabbit and rat right ventricle, at 37 degrees C. 2. At 0.5Hz, 30 microM TBQ induced a marked negative inotropic effect in both species (-57% in the rabbit and -68% in the rat) and decreased the rate of rise and fall of twitch tension. In parallel, SR Ca2+ content (assessed by rapid cooling contractures) was depressed in the rabbit by 42%. The force-frequency relationship (positive for the rabbit and negative for the rat) was significantly attenuated. In the rabbit, this alteration was shown to rely on insufficient SR Ca2+ reloading with increasing frequencies. 3. Exposure of TBQ-treated preparations to 8 mM extracellular Ca2+ or 5 microM isoprenaline were effective in reloading the SR with Ca2+ whereas 20 mM caffeine emptied this compartment. 4. In the rabbit ventricle, increase in stimulation frequency shortened control twitch time course by decreasing both the time to peak tension (TTP) and the time to half relaxation (t1/2). TBQ did not differentially affect the pattern for t1/2 but significantly attenuated the frequency-induced decrease of TTP. 5. In rabbit ventricular muscle, the action potential duration increased between 0.5 and 3 Hz whether or not TBQ was present. However, TBQ induced a small but significant additional action potential shortening. 6. TBQ decreased twitch tension in the rat ventricle between 0.5 and 3 Hz but the negative staircase was not differentially affected by the SR Ca2+ pump inhibitor. In control conditions and in the presence of 30 microM TBQ, t1/2 was frequency-independent but TBQ consistently increased this parameter (by approximately 29%). 7. These data argue in favour of a specific and partial inhibition of the SR Ca2+ pump by 30 microM TBQ in the rabbit and rat ventricle and emphasise the importance of SR Ca2+ uptake in the force-frequency phenomenon.     

The effect of suxamethonium alone and its interaction with gallamine on the indirectly elicited tetanic and single twitch contractions of skeletal muscle in man during anaesthesia

Simultaneous measurements of tetanic and single twitch contractions of the adductor politics muscle in man were made during neuromuscular blockade induced by suxamethonium (0.2 mg/kg) under nitrous oxide, oxygen and pentazocine anaesthesia. 2. After a suitable control period, suxamethonium (0.2 mg/kg) was given intravenously and the same dose was repeated 15 min later. After a further 15 min gallamine (0.2 mg/kg) was administered intravenously. When recovery from gallamine reached a plateau on the tetanic contraction recording a third injection of suxamethonium was given. 3. In most patients, suxamethonium (0.2 mg/kg) caused a partial blockade of the single twitch and complete blockade of the tetanic contraction. In every instance, the tetanic contraction was more depressed and recovered more slowly than the single twitch which not only recovered promptly but also showed overshoot. 4. After gallamine marked antagonism to suxamethonium block developed and this was greater with the single twitch than with the tetanic contractions. 5. Tetanic-tension fade was observed after every injection of suxamethonium and the degree of fade was dependent on the frequency of the tetanic stimulation.     

The size of the subpopulation susceptible to malignant neoplasm of the brain

The effects of acute and chronic glutathione depletion (single i.p. injection of 3 mmol/kg L-buthionine-S,R-sulphoximine and 2 mmol/kg for 4 days) on heart action potential (AP) characteristics, electronmicroscopy, cytochemistry and biochemistry and vascular contractility and nitric oxide-mediated relaxation were studied in rats and guinea pigs. In guinea pig cardiac preparations both acute and chronic glutathione depletion caused a significant decrease of maximum rate of rise of depolarization phase and duration of action potential AP(APD) at 25, 50, and 90% of repolarization but did not modify the other AP parameters. The contractile responses of helically cut aortic strips to norepinephrine were not altered by chronic glutathione depletion but the relaxing responses of precontracted preparations to acetylcholine were significantly reduced both in rats and guinea pigs. Morphologically there were indications of permeability changes, intracellular and interstitial edema and myofilament damage in the myocardium. There was also a decrease in cytochromoxydase and succinyl dehydrogenase activities both in rats and guinea pigs. The present data suggest that glutathione depletion may influence the Na+ and K+ channel activities, causes morphological and biochemical changes in cardiac preparations and may interfere with nitric oxide generation or its action in aortic strips.     

Evaluation of NR-LU-10 with the Neoprobe gamma detector in a mouse model

1. The effects of diethyl maleate (DEM) on the cytotoxicity of phenyl-hydroquinone (PHQ) and other hydroquinones were studied in freshly isolated rat hepatocytes. 2. Addition of PHQ (0.5 or 0.75 mM) to hepatocytes resulted in dose-dependent cell death accompanied by the abrupt depletion of both GSH and protein thiols and the accumulation of phenyl-benzoquinone (PBQ). 3. Pretreatment with DEM (1.25 mM), which causes an abrupt depletion of cellular GSH in hepatocytes, delayed the onset of PHQ-induced cytotoxicity. The delay correlated with inhibition of PBQ formation. 4. Although the pH of the cell suspension was increased slightly (mean pH 0.18) by incubation under carbogen flow, the addition of DEM to the cell suspension inhibited both the increase in pH and the formation of PBQ from PHQ. 5. In hepatocyte suspensions without DEM, PHQ cytotoxicity was dependent on pH, and toxicity was associated with oxidation of PHQ and accumulation of PBQ. 6. Among other hydroquinones (0.5 mM), tert-butyl-hydroquinone-induced cytotoxicity was decreased by DEM (1.25 mM), but DEM did not affect the cytotoxicity of 2,5-di(tert-butyl)-1,4-benzohydroquinone. 7. PHQ-induced cytotoxicity correlated with the accumulation of PBQ in the cell, and the inhibition of PHQ-induced cytotoxicity by DEM correlated with pH-dependent changes in PBQ formation.     

Average but not continuous speed match between motoneurons and muscle units of rat tibialis anterior

1. Properties of single motoneuron/muscle-unit combinations were determined for tibialis anterior (TA) in rats anesthetized with pentobarbital. The TA observations were systematically compared with those obtained earlier by the use of the same techniques from rat medial gastrocnemius (MG). 2. TA motoneurons were investigated with regard to afterhyperpolarization (AHP; total duration 32-74 ms, amplitude 0.39-4.96 mV) and axonal conduction velocity (41-79 m/s). TA muscle-unit measurements included the time course of the isometric twitch (time-to-peak force 10.8-18.0 ms; total duration 42-92 ms), the maximum tetanic force (22-217 mN), and a measure of fatigue sensitivity (fatigue index 5-100%). The range of twitch and AHP durations ("speed range") was markedly smaller in the present TA material than for MG. 3. The mean duration of the TA motoneuronal AHP (49 +/- 8 ms, mean +/- SD) was close to that of its muscle-unit twitch (56 +/- 12 ms). Thus an "average" speed match existed between TA motoneurons and their muscle fibers. 4. For TA there was no correlation between the time courses of AHP and twitch. Thus there was for TA no "continuous" speed match between the motoneurons and their muscle fibers. 5. For TA twitches or AHPs studied separately, there was a significant correlation between different time course measures. Furthermore, compared with TA units having relatively fast twitches, those with slower twitches tended to show 1) a smaller maximum tetanic force and 2) a greater AHP amplitude. Fatigue-resistant units tended to have slower twitches than fatigue-sensitive ones.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inducible NO synthase II and neuronal NO synthase I are constitutively expressed in different structures of guinea pig skeletal muscle: implications for contractile function

The expression of NOS isoforms was studied in guinea pig skeletal muscle at the mRNA and protein level, and the effect of NO on contractile response was examined. Ribonuclease protection analyses demonstrated NOS I and NOS II mRNAs in diaphragm and gastrocnemius muscle. In Western blots, NOS I and NOS II immunoreactivities were found in the particulate but not the soluble fraction of skeletal muscle. NOS activity was found almost exclusively in the particulate fraction. About 50% of this activity was Ca2+ independent. In immunohistochemistry, the anti-NOS I antibody stained distinct membrane regions of muscle fibers. The most intense staining was seen in neuromuscular endplates identified by labeling with alpha-bungarotoxin. The anti-NOS II antibody labeled muscle fibers that contained alkali-labile myosin ATPase (type I fibers). NOS II was located to intracellular structures and was also seen in "specific pathogen-free" animals. Pretreatment of guinea pigs with bacterial lipopolysaccharide (LPS) markedly intensified NOS II staining. Significant NOS III immunoreactivity was detected only in vascular endothelium. In functional experiments, tetanic muscle contractions were induced in diaphragm and gastrocnemius muscle by electrical stimulation of the innervating nerves. Pretreatment of guinea pigs with LPS or addition of S-nitroso-N-acetyl-D,L-penicillamine to the organ bath markedly decreased tetanic contractions. N(G)-nitro-L-arginine, on the other hand, increased contractile force and reversed the effect of LPS. Our data indicate that NOS II and NOS I are expressed in different structures of skeletal muscle and are involved in the regulation of contractile response.     

Influence of applied tension and nitric oxide on responses to endothelins in rat pulmonary resistance arteries: effect of chronic hypoxia

1. The effect of basal tension (transmural tensions 235 +/- 29 mg wt (low tension: equivalent to approximately 16 mmHg) and 305 +/- 34 mg wt (high tension: equivalent to 35 mmHg)) on rat pulmonary resistance artery responses to endothelin-1 (ET-1) and the selective ET(B)-receptor agonist sarafotoxin S6c (S6c) were studied. The effects of nitric oxide synthase inhibition with N(omega)-nitro-L-arginine methylester (L-NAME, 100 microM) on ET receptor-induced responses, as well as vasodilator responses to acetylcholine (ACh) and S6c, were also investigated. Changes with development of pulmonary hypertension, induced by two weeks of chronic hypoxia, were determined. 2. Control rat preparations showed greatest sensitivity for ET-1 when put under low tension (pEC50: 8.1 +/- 0.1) compared with at the higher tension (pEC50: 7.7 +/- 0.1) and there were significant increases in maximum contractile responses to S6c (approximately 80%) and noradrenaline (approximately 60%) when put under high tension. 3. In control pulmonary resistance arteries, both ET-1 and S6c produced potent vasoconstrictor responses. S6c was 12 fold more potent than ET-1 in vessels set at low tension (S6c pEC50: 9.2 +/- 0.1) and 200 fold more potent than ET-1 when the vessels were set at high tension (S6c pEC50: 9.0 +/- 0.1). Chronic hypoxia did not change the potencies of ET-1 and S6c but did significantly increase the maximum contractile response to ET-1 by 60% (at low tension) and 130% (at high tension). 4. In control rat vessels, L-NAME itself caused small increases in vascular tone (5-8 mg wt tension) in 33-56% of vessels. In the chronic hypoxic rats, in vessels set at high tension, L-NAME-induced tone was evident in 88% of vessels and had increased to 26.9 +/- 6.6 mg wt tension. Vasodilatation to sodium nitroprusside, in non-preconstricted vessels, was small in control rat vessels (2-6 mg wt tension) but increased significantly to 22.5 +/- 8.0 mg wt tension in chronic hypoxic vessels set at the higher tensions. Together, these results indicate an increase in endogenous tone in the vessels from the chronic hypoxic rats which is normally attenuated by nitric oxide production. 5. L-NAME increased the sensitivity to S6c 10 fold (low tension) and 6 fold (high tension) only in chronic hypoxic rat pulmonary resistance arteries. It had no effect on responses to ET-1 in any vessel studied. 6. Vasodilatation of pre-contracted vessels by ACh was markedly greater in the pulmonary resistance arteries from the chronic hypoxic rats (pIC50: 7.12 +/- 0.19, maximum: 72.1 +/- 0.2.0%) compared to their age-matched controls (pIC50: 5.77 +/- 0.15, maximum: 28.2 +/- 2.0%). There was also a 2.5 fold increase in maximum vasodilatation induced by ACh. 7. These results demonstrate that control rat preparations showed greatest sensitivity for ET-1 when set at the lower tension, equivalent to the pressure expected in vivo (approximately 16 mmHg). Pulmonary hypertension due to chronic hypoxia potentiated the maximum response to ET-1. Pulmonary resistance arteries from control animals exhibited little endogenous tone, but exposure to chronic hypoxia increased endogenous inherent tone which is normally attenuated by nitric oxide. Endogenous nitric oxide production may increase in pulmonary resistance arteries from chronic hypoxic rats and attenuate contractile responses to ET(B2) receptor stimulation. Relaxation to ACh was increased in pulmonary resistance arteries from chronic hypoxic rats.     

Extraocular motor unit and whole-muscle responses in the lateral rectus muscle of the squirrel monkey

Because primate studies provide data for the current experimental models of the human oculomotor system, we investigated the relationship of lateral rectus muscle motoneuron firing to muscle unit contractile characteristics in the squirrel monkey. Also examined was the correlation of whole-muscle contractile force with the degree of evoked eye displacement. A force transducer was used to record lateral rectus whole-muscle or muscle unit contraction in response to abducens whole-nerve stimulation or stimulation of single abducens motoneurons or axons. Horizontal eye displacement was recorded using a magnetic search coil. (1) Motor units could be categorized based on contraction speed (fusion frequency) and fatigue. (2) The kt value (change in motoneuronal firing necessary to increase motor unit force by 1.0 mg) of the units correlated with maximum tetanic tension. (3) There was some tendency for maximum tetanic tension of this unit population to separate into three groups. (4) At a constant frequency of 100 Hz, 95% of the motor units demonstrated significantly different force levels dependent on immediately previous stimulation history (hysteresis). (5) A mean force change of 0.32 gm/ degrees and a mean frequency change of 4.7 Hz/ degrees of eye displacement were observed in response to whole-nerve stimulation. These quantitative data provide the first contractile measures of primate extraocular motor units. Models of eye movement dynamics may need to consider the nonlinear transformations observed between stimulation rate and muscle tension as well as the probability that as few as two to three motor units can deviate the eye 1 degrees.     

GTP-binding protein regulates the contractile response elicited by the phorbol ester (PMA)-induced activation of protein kinase C in the isolated rat aorta

1. The aim of the present study was to investigate the involvement of GTP-binding protein in the contractile response induced by activation of protein kinase C (PKC) in isolated rat aorta. The rats were treated with islet-activating protein (IAP) for 4 days prior to the experiments. 2. In the aorta from control rats, phorbol 12-myristate 13-acetate (PMA) produced biphasic contractions; twitch contraction superimposed on the slowly developing contraction. The twitch contraction was abolished by the removal of external Ca2+ or by treatment with nicardipine. In the aorta pretreated with IAP, PMA produced only a slowly developing contraction, and no twitch contraction was induced. 3. The application of Ca2+ to aortic strips in a Ca(2+)-free solution, that had been treated with 10(-6) M PMA caused concentration-dependent contraction, and the contraction was completely inhibited by IAP. 4. Pretreatment with IAP inhibited Ca(2+)-induced contraction of the aorta in Ca(2+)-free medium in the presence of 10(-6) M clonidine, but did not affect the Ca(2+)-induced contraction in the medium treated with 10(-6) M phenylephrine and 10(-7) M nicardipine. 5. These results suggest that the activation of PKC by PMA produces biphasic contractions in the rat aorta. The twitch contraction may be induced by the activation of voltage-dependent Ca(2+)-channels and the activation may be regulated by IAP-sensitive GTP-binding protein.     

The effect of acute hypoxia on the dynamic formation of unfused tetanus in the rat extensor digitorum longus

The effect of acute hypoxia on a single twitch and tetanic twitch parameters, was studied. The postactivation phase was found to be independent of the oxygen delivery.