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1.
We examined 1) whether the effects of lowered trans-sarcolemmal Na+ gradient on force differed between nonfatigued fast- and slow-twitch muscles of mice and 2) whether effects on action potentials could explain the decrease of force. The Na+ gradient was reduced by lowering the extracellular [Na+] ([Na+]o). The peak force-[Na+]o relationships for the twitch and tetanus were the same in nonfatigued extensor digitorum longus and soleus muscles: force was maintained over a large range of [Na+]o and then decreased abruptly over a much smaller range. However, fatigue was significantly exacerbated at a lowered [Na+]o that had little effect in nonfatigued soleus muscle. This finding suggests that substantial differences exist in the Na+ effect on force between nonfatigued and fatigued muscle. The reduced contractility in nonfatigued muscles at lowered [Na+]o was largely due to 1) an increased number of inexcitable fibers and threshold for action potentials, 2) a reduction of action potential amplitude, and 3) a reduced capacity to generate action potentials throughout trains. sodium gradient; muscle contraction; action potential train; extensor digitorum longus; soleus  相似文献   

2.
A Study of the Reinnervation of Fast and Slow Mammalian Muscles   总被引:9,自引:0,他引:9       下载免费PDF全文
Miniature end plate potential (mepp) frequency in innervated extensor muscle is significantly higher than in soleus muscle. 9 days after nerve crush mepps of low amplitude and prolonged duration reappeared at a frequency of 2% of control and were similar to normal muscles after 35 days. Membrane potential began to increase 9–10 days after nerve crush and at 30 days was similar to controls. The region most sensitive to ACh in denervated and reinnervated muscles was the end plate. Caffeine (20 mM, 23°C) induced contracture in innervated soleus but not in extensor muscles. After denervation the extensor became sensitive to caffeine while the soleus muscles decreased in sensitivity to the drug; 4–5 days after reinnervation the effect of caffeine on these muscles was similar to control. The events during reinnervation are: (a) reappearance of mepps at the same time as end plate potential and muscle twitch; (b) partial restoration of the membrane potential; (c) return of caffeine-induced contracture to normal levels in the soleus and its absence in the extensor muscles; (d) return of membrane resistance to normal values in both muscles at about 25 days; and (e) return of ACh-sensitivity to control levels at about 30 days in both muscles. Although these results suggest that the membrane potential and sarcoplasmic reticulum are under neural influence, it remains to be established whether or not separate neurotrophic factors are involved.  相似文献   

3.
The objective of this study was to determine whether an increased duration of the action potential contributes to the K+-induced twitch potentiation at 37 degrees C. Twitch contractions were elicited by field stimulation, and action potentials were measured with conventional microelectrodes. For mouse extensor digitorum longus (EDL) muscle, twitch force was greater at 7-13 mM K+ than at 4.7 mM (control). For soleus muscle, twitch force potentiation was observed between 7 and 11 mM K+. Time to peak and half-relaxation time were not affected by the increase in extracellular K+ concentration in EDL muscle, whereas both parameters became significantly longer in soleus muscle. Decrease in overshoot and prolongation of the action potential duration observed at 9 and 11 mM K+ were mimicked when muscles were respectively exposed to 25 and 50 nM tetrodotoxin (TTX; used to partially block Na+ channels). Despite similar action potentials, twitch force was not potentiated by TTX. It is therefore suggested that the K+-induced potentiation of the twitch in EDL muscle is not due to a prolongation of the action potential and contraction time, whereas a longer contraction, especially the relaxation phase, may contribute to the potentiation in soleus muscle.  相似文献   

4.
The diaphragm muscle of hyperkalemic periodic paralysis (HyperKPP) patients and of the M1592V HyperKPP mouse model rarely suffers from the myotonic and paralytic symptoms that occur in limb muscles. Enigmatically, HyperKPP diaphragm expresses the mutant NaV1.4 channel and, more importantly, has an abnormally high Na+ influx similar to that in extensor digitorum longus (EDL) and soleus, two hindlimb muscles suffering from the robust HyperKPP abnormalities. The objective was to uncover the physiological mechanisms that render HyperKPP diaphragm asymptomatic. A first mechanism involves efficient maintenance of resting membrane polarization in HyperKPP diaphragm at various extracellular K+ concentrations compared with larger membrane depolarizations in HyperKPP EDL and soleus. The improved resting membrane potential (EM) results from significantly increased Na+ K+ pump electrogenic activity, and not from an increased protein content. Action potential amplitude was greater in HyperKPP diaphragm than in HyperKPP soleus and EDL, providing a second mechanism for the asymptomatic behavior of the HyperKPP diaphragm. One suggested mechanism for the greater action potential amplitude is lower intracellular Na+ concentration because of greater Na+ K+ pump activity, allowing better Na+ current during the action potential depolarization phase. Finally, HyperKPP diaphragm had a greater capacity to generate force at depolarized EM compared with wild-type diaphragm. Action potential amplitude was not different between wild-type and HyperKPP diaphragm. There was also no evidence for an increased activity of the Na+–Ca2+ exchanger working in the reverse mode in the HyperKPP diaphragm compared with the wild-type diaphragm. So, a third mechanism remains to be elucidated to fully understand how HyperKPP diaphragm generates more force compared with wild type. Although the mechanism for the greater force at depolarized resting EM remains to be determined, this study provides support for the modulation of the Na+ K+ pump as a component of therapy to alleviate weakness in HyperKPP.  相似文献   

5.
Action potentials (APs) were recorded from the extrajunctional membrane of surface fibers of the fast-twitch extensor digitorum longus (extensor) and the slow-twitch soleus muscles of adult rats. APs of the extensor muscle had a significantly faster rate of rise and fall, as well as a shorter duration, than those of the soleus. In addition, the overshoot of APs and the resting membrane potential was greater for the extensor. Whereas the soleus produced only one AP regardless of the stimulus duration, the number of extensor responses was directly proportional to the stimulus duration. This repetitive activity was greatly reduced by a concentration of tetrodotoxin (TTX) as low as 5 X 10(11) g/ml. Within 8 d after crush of the nerves to these two muscles, all differences in AP properties disappeared and both muscles became partially resistant to TTX. Reinnervation brought about a redifferentiation so that differences in AP were again significant at 22 d after nerve crush. However, the rate of rise of extensor APs did not attain normal values even as late as 60 d after nerve crush. APs were found to be the same for extensor and soleus muscles from 12-d-old rats. At 18 d after birth, rate of rise was equivalent to that of adult muscle for the soleus although 50--60 d were required before this parameter was fully mature for the extensor. Nevertheless, APs of the extensor and soleus were clearly differentiated within 25 d after birth. Differences in fast and slow muscle APs are discussed with regard to differences in ion gradients and sarcolemmal conductance.  相似文献   

6.
The action of the tranquilizer diazepam on rat skeletal muscle showed that relaxation of isometric twitches is controlled by different processes in extensor digitorum longus (fast-twitch) and soleus (slow-twitch) muscles. Diazepam caused an increase in the amplitude of twitches in fibres from both muscles but increased the twitch duration only in soleus. The amplitude of fused tetani were reduced in both muscles and the rate of relaxation after the tetanus slowed by as much as 34% when the amplitude of the tetanus was reduced by only 11%. The slower tetanic relaxation indicated that calcium uptake by the sarcoplasmic reticulum was slower than normal in slow- and fast-twitch fibres. We conclude therefore that calcium uptake by the sarcoplasmic reticulum is rate limiting for twitch relaxation in slow-twitch but not fast-twitch fibres and suggest that calcium binding to parvalbumin controls relaxation in the fast fibres.  相似文献   

7.
Fast (extensor digitorum longus) and slow (soleus) rat skeletal muscles served as the source for isolation and biochemical comparison of two distinct surface membrane fractions with properties of the sarcolemma and transverse tubular system. Enriched sarcolemmal membrane from soleus demonstrated a lighter density after sucrose density centrifugation. Sialic acid content was 1.5-fold higher in soleus (62 nmol/mg) than extensor (40 nmol/mg). The specific activity of (Na+ + K+ + Mg2+)-ATPase was similar (1.40 and 1.65 micronmol Pi/mg per 5 min) with the soleus enzyme displaying a (1) greater resistance to inhibition by ouabain, and (2) broader ionic ratio (Na+/K+) requirement than extensor enzyme. The polypeptide and phospholipid composition showed no major differences between the two muscle types. The second surface membrane fraction, tentatively identified as transverse tubule, differed in membrane composition. The major polypeptide of extensor was of 95 000 molecular weight whereas for soleus a Mr=28 000 species was dominant. Total phospholipid content of soleus was 1.5-fold greater than extensor due mostly to increased levels of phosphatidylcholine and phosphatidylethanolamine. Endogenous membrane protein kinase for the 28 000 molecular weight polypeptide was found exclusively in this membrane. The reaction conditions were identical for extensor and soleus since both required divalent cations (Ca2+ and Mg2+) and neither was affected by cyclic AMP. Soleus showed a 2-fold higher capacity for phosphate incorporation than extensor. These studies show that surface membrane fractions derived from fast and slow muscles differ in terms of functional and compositional properties. These differences are specific not only for the surface membrane but for the muscle type and may relate to the known physiological differences observed between fast and slow mammalian muscle.  相似文献   

8.
The metabolic integrity of fully regenerated transplants was investigated by measuring induced changes in glycogen concentration. The extensor digitorum longus and the soleus muscles were cross transplanted: the extensor digitorum longus into the soleus muscle bed (SOLT) and the soleus muscle into the extensor digitorum longus bed (EDLT). The histochemical fiber type distribution of the regenerated muscles was determined and was found to transform in cross-transplanted EDLT and SOLT. After transplantation and regeneration, both muscles had initially low glycogen concentrations. However, the EDLT glycogen concentration was not significantly different from that of the contralateral extensor digitorum longus control muscle after 60 days. In the SOLT, glycogen gradually increased but remained less than in the contralateral soleus control muscle. SOLT and control soleus muscles responded with a significant glycogen depletion to an epinephrine dose two orders of magnitude less than the lowest dose affecting glycogen levels in EDLT and extensor digitorum longus muscles. These results indicate that transplanted muscles are capable of regenerating normal glycogenolytic responses and that the sensitivity of the response observed depends on the site of transplantation and is related to the type of innervation and histochemical fiber type.  相似文献   

9.
With increasing pulse rate (up to 150 square pulses/sec) applied for 1 second at the gastrocnemius and soleus muscle the amplitude of electromyographic response was found to decrease. An amplitude decrease of sum action potentials (AP) recorded from the muscle surface occurred already at pulse rates below 100 pulses/sec. For the gastrocnemius muscle, this amplitude fall in the medium pulse-rate region can be described by the relation: amplitude = -log-pulse rate. At the soleus muscle, the amplitude fall is shifted towards the higher frequencies. After intensive swimming of the animal the amplitude depression of AP at the gastrocnemius muscle occurs already at a lower rate, and departs from the aforementioned relation. The causes are looked for in the differential properties of the various muscle fibres.  相似文献   

10.
1. Rats were treated with dexamethasone for 4 days before measurement of the rates of lactate formation [which is an index of hexose transport; see Challiss, Lozeman, Leighton & Newsholme (1986) Biochem. J. 233, 377-381] and glycogen synthesis in response to various concentrations of insulin in isolated incubated soleus and extensor digitorum longus muscle preparations. 2. The concentration of insulin required to stimulate these processes half-maximally in soleus and extensor digitorum longus muscles isolated from control rats was about 100 muunits/ml. 3. Dexamethasone increases the concentration of insulin required to stimulate glycolysis half-maximally in soleus and extensor digitorum longus preparations to 250 and 300 muunits/ml respectively. The respective insulin concentrations necessary to stimulate glycogen synthesis half-maximally were about 430 and 370 muunits/ml for soleus and extensor digitorum longus muscle preparations isolated from steroid-treated rats. 5. Dexamethasone treatment did not change the amount of insulin bound to soleus muscle.  相似文献   

11.
Fast (extensor digitorum longus) and slow (soleus) rat skeletal muscles served as the source for isolation and biochemical comparison of two distinct surface membrane fractions with properties of the sarcolemma and transverse tubular system. Enriched sarcolemmal membrane from soleus demonstrated a lighter density after sucrose density centrifugation. Sialic acid content was 1.5-fold higher in soleus (62 nmol/mg) than extensor (40 nmol/mg). The specific activity of (Na+ + K+ + Mg2+)-ATPase was similar (1.40 and 1.65 μmol Pi/mg per 5 min) with the soleus enzyme displaying a (1) greater resistance to inhibition by ouabain, and (2) broader ionic ratio (Na+K+) requirement than extensor enzyme. The polypeptide and phospholipid composition showed no major differences between the two muscle types.The second surface membrane fraction, tentatively identified as transverse tubule, differed in membrane composition. The major polypeptide of extensor was of 95 000 molecular weight whereas for soleus a Mr = 28 000 species was dominant. Total phospholipid content of soleus was 1.5-fold greater than extensor due mostly to increased levels of phosphatidylcholine and phosphatidylethanolamine. Endogenous membrane protein kinase for the 28 000 molecular weight polypeptide was found exclusively in this membrane. The reaction conditions were identical for extensor and soleus since both required divalent cations (Ca2+ and Mg2+) and neither was affected by cyclic AMP. Soleus showed a 2-fold higher capacity for phosphate incorporation than extensor.These studies show that surface membrane fractions derived from fast and slow muscles differ in terms of functional and compositional properties. These differences are specific not only for the surface membrane but for the muscle type and may relate to the known physiological differences observed between fast and slow mammalian muscle.  相似文献   

12.
We examined whether electrical field stimulation with varying characteristics could excite isolated mammalian skeletal muscle through different sites. Supramaximal (20-V, 0.1-ms) pulse stimulation with transverse wire or parallel plate electrodes evoked similar forces in nonfatigued slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles from mice. d-tubocurarine shifted the twitch force-stimulation strength relationship toward higher pulse strengths with both electrode configurations in soleus muscle, suggesting that weaker pulses excite muscle via neuromuscular transmission. With wire stimulation, movement of the recording electrode along the muscle caused a delay between the stimulus artifact and the peak of the action potential, consistent with action potential propagation along the sarcolemma. TTX abolished all contractions evoked with 20-V, 0.1-ms pulses, suggesting that excitation occurred via voltage-dependent Na+ channels and, hence, muscle action potentials. TTX did not prevent force development with > or = 0.4-ms pulses in soleus or 1-ms pulses in EDL muscle. Furthermore, myoplasmic Ca2+ (i.e., the fura 2 ratio) and sarcomere shortening were greater during tetanic stimulation with 2.0-ms than with 0.5-ms pulses in flexor digitorum brevis fibers from rats. TTX prevented all shortening and Ca2+ release with 0.5-ms, but not 2.0-ms, pulses, indicating that longer pulses can directly trigger Ca2+ release. Hence, proper interpretation of mechanistic studies requires precise understanding of how muscles are excited; otherwise, incorrect conclusions can be made. Using this new understanding, we showed that disrupted propagation of action potentials along the surface membrane is a major cause of fatigue in soleus muscle that is focally and continuously stimulated at 125 Hz.  相似文献   

13.
Insulin binding, insulin degradation, and 2-deoxyglucose uptake were examined at 18 and 37 degrees C in soleus and extensor digitorum longus muscles of mice. Insulin binding and degradation were greater in the soleus than in the extensor digitorum longus at both temperatures (p less than 0.05). At 37 degrees C, binding was decreased in both muscles while percentage degradation was increased in comparison with 18 degrees C (p less than 0.05). Dose--response curves (percentage of binding at 4 nM of insulin) remained the same for both muscles at the two temperatures. Basal (no insulin) 2-deoxyglucose uptake was increased at 37 degrees C in the extensor digitorum longus but not the soleus. Insulin responsiveness in terms of the amount of 2-deoxyglucose taken up per femtomole of insulin bound was almost identical for the two muscles at 18 degrees C, whereas at 37 degrees C it was increased more in the soleus than in the extensor digitorum longus. The results indicate that in the presence of physiological concentrations of insulin (0.2-4 nM), insulin binding trends are minimally affected by increased temperature. In contrast, the ability of insulin to stimulate 2-deoxyglucose uptake varies between the two temperatures, and at the higher temperature between fast- and slow-twitch muscle.  相似文献   

14.
Single muscle fibers were isolated from soleus and extensor digitorum longus muscle of adult rats. The muscle fiber type of single fibers was determined physiologically by the skinned fiber method according to the sensitivity to strontium (Sr) ions. The fiber type of single fibers was contrasted to the pattern of myosin light chains analyzed by one and two dimensional gel-electrophoreses. All the type 2 fibers isolated from soleus muscle contained both fast and slow types of myosin light chains.  相似文献   

15.
The effects of 5 weeks treadmill-exercise training on isometric tension and contractile proteins were studied in intact and skinned isolated small bundles of rat skeletal soleus and extensor digitorum longus (edl) fibers. In soleus and edl muscles, 5 weeks exercise training: (i) increased twitch amplitude by 25% and 8%, respectively, without modification in the time-to-peak tension and the time constant of relaxation, (ii) increased the amplitude of K(+) contracture by 93% and 88%, respectively, and accelerated its relaxation by 17% and 43%, respectively, and (iii) increased the amplitude of caffeine contractures (soleus: 0.5 mM: 86%, 10 mM: 77%; edl: 0.5 mM: 89%, 10 mM: 87%). In conclusion, changes in contractile responses were associated with shifts in the steady state inactivation curves and in the voltage-dependent activation curve to a more negative potential, with increases in soleus and edl caffeine sensitivity, without changes in the Ca(2+) sensitivity of contractile proteins and myosin heavy chain isoforms.  相似文献   

16.
Inactivation of excitation-contraction coupling was examined in extensor digitorum longus (EDL) and soleus muscle fibers from rats injected daily with tri-iodothyronine (T3, 150 micrograms/kg) for 10-14 d. Steady-state activation and inactivation curves for contraction were obtained from measurements of peak potassium contracture tension at different surface membrane potentials. The experiments tested the hypothesis that noninactivating tension is a "window" tension caused by the overlap of the activation and inactivation curves. Changes in the amplitude and voltage dependence of noninactivating tension should be predicted by the changes in the activation and inactivation curves, if noninactivating tension arises from their overlap. After T3 treatment, the area of overlap increased in EDL fibers and decreased in soleus fibers and the overlap region was shifted to more negative potentials in both muscles. Noninactivating tension also appeared at more negative membrane potentials after T3 treatment in both EDL and soleus fibers. The effects of T3 treatment were confirmed with a two microelectrode voltage-clamp technique: at the resting membrane potential (-80 mV) contraction in response to a brief test pulse required less than normal depolarization in EDL, but more than normal depolarization in soleus fibers. After T3 treatment, the increase in contraction threshold at depolarized holding potentials (attributed to inactivation) occurred at more depolarized holding potentials in EDL, or less depolarized holding potentials in soleus. The changes in contraction threshold could be accounted for by the effects of T3 on the activation and inactivation curves. In conclusion, (a) T3 appeared to affect the expression of both activation and inactivation characteristics, but the activation effects could not be cleanly distinguished from T3 effects on the sarcoplasmic reticulum and contractile proteins, and (b) the experiments provided evidence for the hypothesis that the noninactivating tension is a steady-state "window" tension.  相似文献   

17.
Although ATP-sensitive K+ (KATP) channel openers depress force, channel blockers have no effect. Furthermore, the effects of channel openers on single action potentials are quite small. These facts raise questions as to whether 1) channel openers reduce force via an activation of KATP channels or via some nonspecific effects and 2) the reduction in force by KATP channels operates by changes in amplitude and duration of the action potential. To answer the first question we tested the hypothesis that pinacidil, a channel opener, does not affect force during fatigue in muscles of Kir6.2-/- mice that have no cell membrane KATP channel activity. When wild-type extensor digitorum longus (EDL) and soleus muscles were stimulated to fatigue with one tetanus per second, pinacidil increased the rate at which force decreased, prevented a rise in resting tension, and improved force recovery. Pinacidil had none of these effects in Kir6.2-/- muscles. To answer the second question, we tested the hypothesis that the effects of KATP channels on membrane excitability are greater during action potential trains than on single action potentials, especially during metabolic stress such as fatigue. During fatigue, M wave areas of control soleus remained constant for 90 s, suggesting no change in action potential amplitude for half of the fatigue period. In the presence of pinacidil, the decrease in M wave areas became significant within 30 s, during which time the rate of fatigue also became significantly faster compared with control muscles. It is therefore concluded that, once activated, KATP channels depress force and that this depression involves a reduction in action potential amplitude. Kir6.2-/- mice; pinacidil; action potential train; M wave  相似文献   

18.
Summary Glucose-6-phosphate dehydrogenase activity increases following denervation of rat skeletal muscle. The specificity of this effect to muscle fibre type was studied. Basal activity of the dehydrogenase was higher in soleus, a muscle composed predominantly of type I fibres, than in extensor digitorum longus, a muscle composed predominantly of type IIa and b fibres. The enzymatic activity of the soleus was also greater than that of the red (RQ) and white (WQ) portions of quadriceps muscle (predominantly type IIa and type IIb fibres, respectively). Following denervation, glucose-6-phosphate dehydrogenase increased in extensor digitorum longus and RQ, but not in WQ or the soleus. Following chronic treatment of rats with 3,3,5-triiodothyronine, which converts type I muscle fibres to type II, the dehydrogenase activity increased in both denervated soleus and extensor digitorum longus. It is concluded that the effect of denervation on glucose-6-phosphate dehydrogenase activity is selective for type IIa (fast oxidative-glycolytic) muscle fibres.  相似文献   

19.
1. Thiamine diphosphate level was higher in soleus muscle than in extensor digitorum longus muscle in various animals, whereas thiamine triphosphate level was less in the former muscle than in the latter except for mouse. 2. 2-Oxoglutarate dehydrogenase, transketolase and thiamine pyrophosphokinase activities were higher in soleus muscle than in extensor digitorum longus in rat and guinea pig. 3. The differences between rat two muscle phenotypes in thiamine diphosphate, but not thiamine triphosphate, level and the thiamine-related enzyme activities disappeared after denervation. 4. Tenotomy had little effect on thiamine phosphate levels and the thiamine-related enzyme activities in rat skeletal muscles.  相似文献   

20.
We tested the effects of inhibiting the carbonic anhydrase activity of rat soleus and extensor digitorum longus muscles on the isometric contractile properties and the resistance to fatigue. SOL and EDL muscles from female rats were incubated in vitro in the presence of methazolamide, a specific inhibitor of carbonic anhydrase, before determining their contractile properties. Methazolamide had no effects on the contractile properties of the soleus muscle (10(-5) or 10(-3) M) and extensor digitorum longus (10(-3) M), except for the half-relaxation time of the soleus muscle which increased significantly. Values for half-relaxation time were significantly increased with both concentrations of the inhibitor. Muscles were then submitted to a fatigue protocol lasting 30 min. During the fatigue test, no significant difference was observed between control and 10(-5) M methazolamide soleus muscles. In presence of 10(-3) M methazolamide however, the soleus muscle showed a significantly increased resistance to fatigue compared with control preparations. No significant effect was observed with the extensor digitorum longus muscle exposed to 10(-3) M methazolamide. Results are discussed in terms of the presence of two different isoforms of carbonic anhydrase that may be associated with calcium uptake and energy metabolic processes, respectively.  相似文献   

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