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CELLULAR METABOLISM
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Submitted 18 November 2005 ; accepted in final form 2 February 2006
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ABSTRACT |
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ATP – PCr + [1.5lactate]). During contractions (2–10 s), BTS decreased force production to 
5% of control. Under these conditions, BTS inhibited ATP turnover by only 18–25%. ATP turnover decreased markedly and similarly with and without BTS as the duration of contraction progressed. In conclusion, cross bridges (i.e., actomyosin ATPase) account for only a small fraction (20%) of the ATP consumption during contraction in mouse fast-twitch skeletal muscle under near-physiological conditions, suggesting that ion pumping is the major energy-consuming process. ATPase; high-energy phosphates; lactate
Recently, N-benzyl-p-toluene sulfonamide (BTS) was identified as a highly specific inhibitor of myosin II ATPase that does not interfere with skeletal muscle Ca2+ handling (3, 5, 29, 35, 46). We have therefore used BTS to assess cross-bridge ATP consumption during isometric contraction in intact muscle preparations under near-physiological conditions (stimulation frequency of 50–70 Hz, 30°C). Under these conditions, cross-bridge ATP consumption in mouse fast-twitch muscle accounts for only 20% of the total ATP consumption.
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METHODS |
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Male NMRI strain mice (30 g) and Wistar rats (100 g) were housed at room temperature with 12:12-h light-dark cycle. Food and water were ingested ad libitum. Animals were euthanized by rapid cervical dislocation and thereafter extensor digitorum longus (EDL) and soleus muscles were isolated. The Stockholm North local ethical committee approved all animal care procedures.
Mounting, solution, and stimulation.
Stainless steel hooks were tied with nylon thread to the muscle tendons. The muscles were then transferred to a stimulation chamber (World Precision Instruments) and mounted in between a force transducer and an adjustable holder. The chamber temperature was set at 30°C with a water-jacketed circulation bath in all but one of the experiments, which was performed at 15°C. We measured the temperature of mouse leg muscles in situ to be 35.1 ± 0.3°C (n = 8), but chose to perform most of our experiments at 30°C. This is because in preliminary experiments, we found that muscle force production decreased by 10% in 20 min, whereas at 30°C, force production remained stable (see below). The muscle was bathed in a Tyrode solution of the following composition (in mM): 121 NaCl, 5 KCl, 1.8 CaCl2, 0.4 NaH2PO4, 0.5 MgCl2, 24 NaHCO3, 0.1 EDTA, 5.5 glucose, and 0.1% fetal calf serum. The solution was continuously gassed with 5% CO2-95% O2, which results in a pH of 7.4. Muscles were stimulated with current pulses (0.5-ms duration; 150% of the voltage required for maximum force response) via plate electrodes lying parallel to the fibers. The muscle was set to the length where maximum tetanic force was produced. Thereafter, a small volume of a BTS stock solution (in DMSO) was added to the chamber, yielding a final concentration of 25 µM; contralateral control muscles received an equivalent volume of DMSO (final concentration = 0.05% vol/vol).
In all experiments, muscles were incubated for 60 min in the absence or presence of BTS before initiation of stimulations. In one series of experiments, muscles were frozen in liquid N2 after the 60-min incubation period (nonstimulated). In another series, following the 60-min incubation period, muscles were stimulated to perform isometric contractions (EDL, 300-ms tetanic duration and soleus, 600-ms tetanic duration at 1-min intervals) to generate force-frequency curves.
Different stimulation protocols were used before the stimulated muscles were frozen. First, EDL muscles were stimulated to perform continuous tetanic contractions (50 Hz, tetanic duration of 2–10 s) in the presence of 2 mM Na+ cyanide (NaCN). Second, fatigue was induced by repeated tetani: 70 Hz, 300-ms tetanic duration, 1 train/2 s for a total of 50 tetani in EDL; 50 Hz, 600-ms tetanic duration, 1 train/2 s for a total of 100 tetani in soleus in the absence or presence of NaCN. NaCN was added 5 min before onset of stimulation to eliminate mitochondrial O2 utilization (19). CN-mediated inhibition of O2 consumption in isolated human and mouse skeletal muscle preparations occurs with Ki values that range from 5 to 10 µM (21, 45) and is complete at a concentration of 1 mM (28). Therefore, it is likely that mitochondrial respiration was fully inhibited by 2 mM NaCN in the present study. Immediately after the last stimulation pulse, the chamber was lowered (<1 s), leaving the muscle suspended in the air between the force transducer and the adjustable holder. The muscle was then detached and frozen in liquid N2 (<5 s). With this procedure the metabolite values in the frozen muscle represent those at the end of contraction because lactate release from the muscle is stopped, whereas phosphocreatine (PCr) resynthesis, an O2-dependent process (34), is prevented by the NaCN.
Analysis. Force signals were sampled on-line and stored in a desktop computer for subsequent analysis. The muscles were stored in liquid N2 until they were freeze dried. The hooks were removed and the muscles were dissected free of the nonmuscle constituents and powdered. The powder was thoroughly mixed and aliquoted.
For analysis of glycogen, aliquots of powder were digested with hot 1 N KOH and hydrolyzed enzymatically to free glucose. Glucose was then analyzed enzymatically with a fluorometric technique (26). For analysis of metabolites, ice-cold 0.5 M perchloric acid was added to aliquots of muscle powder. The extract was kept in an ice bath for 15 min while being agitated with a vortex mixer and then centrifuged (10,000 g). The supernatant was neutralized with 2.2 M KHCO3 and again centrifuged. The latter supernatant was assayed for PCr, Cr, ATP, Pi, glucose 6-P, lactate, and malate with enzymatic techniques [changes in NAD(P)H] adapted for fluorometry (26). In some experiments, lactate was also analyzed in the medium. To adjust for variability in solid nonmuscle constituents, metabolite values were divided by the sum of PCr + Cr (total Cr) and then multiplied by the mean total creatine content for the whole material. BTS did not significantly affect total creatine under any condition (data not shown). Total creatine averaged 90 ± 2 to 107 ± 3 µmol/g dry wt in EDL in the different series of experiments, and 60 ± 4 and 71 ± 2 for mouse and rat soleus, respectively.
ATP turnover was calculated from the following equation: –2ATP – PCr + (1.5 lactate), as we have used earlier (18–20), where refers to the mean contraction value minus the mean basal value. The same basal values (see Table 1) were used for all ATP turnover calculations at 30°C. With the use of this formula, it is assumed that 1) glycogen is the sole source for lactate production (hence 1.5 mol ATP per mol of lactate produced) during short-term intense contractions; 2) the decreases in ATP are associated with stoichiometic increases in inosine 5'-monophosphate in isolated mouse EDL muscle (19), thereby justifying the term –2ATP; and 3) there is no ATP production from oxidative phosphorylation.
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RESULTS |
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80% MHC IIb; 20% MHC IIx/IId) (27). In contrast, the effect of BTS was markedly diminished, but still significant in mouse soleus muscle (Fig. 1C). We reasoned that the large residual effect of BTS was the consequence of a significant proportion (40%) of fast-twitch fibers in soleus muscle of NMRI mice (27). To examine this possibility, additional experiments were performed on rat soleus muscle, which contains relatively few fast-twitch fibers (10–20%) (39). Indeed, the BTS effect was markedly diminished and in general BTS inhibited <20% of force in rat soleus muscles (Fig. 1E).
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Continuous tetani with NaCN at 15°C. We first employed conditions traditionally used to distinguish between relative cross-bridge and SR-Ca2+ ATP utilization (low temperature and high force). Accordingly, muscles were studied at 15°C and stimulated at 50 Hz, which resulted in near-maximal tetanic force (24, 32). Muscles were incubated for 60 min in the absence or presence of BTS and were then either frozen (basal) or stimulated continuously for 2 s. Representative force recordings are presented in Fig. 2. In contrast to the almost complete inhibition of force production by BTS at 30°C, BTS inhibited the force-time integral by 77.9 ± 3.6% (n = 6) at 15°C. BTS had no significant effect on high-energy phosphates or lactate in the basal state (Fig. 3). After contraction, there was an attenuated increase in lactate and decrease in PCr in the BTS-treated muscles, whereas ATP remained stable during contraction in both groups. ATP turnover averaged 28.3 µmol/g dry wt during control and 16.6 during BTS. Correcting for residual force, cross bridges accounted for 53% of the total ATP consumption during the 2-s contraction at 15°C {[(28.3 – 16.6)/28.3] x [100/77.9] x 100%}. Thus BTS yielded results that were comparable to those obtained with other techniques under similar experimental conditions.
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35% of maximal force is obtained (Fig. 1, A and B). Muscles were treated as at 15°C, with the exception that in addition to the 2-s continuous contraction, 5- and 10-s contractions were also performed. Representative force recordings from 10-s contractions are presented in Fig. 4. The force x time integrals in BTS averaged 6 ± 1, 4 ± 1, and 5 ± 1% of the values obtained during control conditions during the 2-, 5-, and 10-s contractions (n = 6), respectively. BTS had no significant effect on glycogen, glycolytic intermediates, malate, ATP, or Pi in the basal state (Table 1). However, BTS resulted in a small (5%) but statistically significant increase in PCr and corresponding decrease in Cr. During the shorter tetani (2 and 5 s), PCr degradation and Pi and lactate accumulation were significantly diminished by BTS (Table 2). By 10 s, there were no longer any significant differences in PCr and lactate levels among the groups. However, at 10 s, ATP was markedly decreased in control, but not in BTS. The inhibition of ATP depletion by BTS was associated with a smaller accumulation of Pi, although PCr values were similar in the two groups.
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20%, whereas force production was decreased by 95% (Fig. 5). Moreover, ATP turnover rates decreased markedly during the continuous tetani during control and similar relative decreases were seen in the BTS-treated muscles (Table 3).
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5-fold (to 0.49 ± 0.04 and 0.55 ± 0.07 µmol/g dry wt in control and BTS, respectively; P > 0.05 between groups; n = 6). As expected, muscles exhibited a large degree of anaerobic metabolism, as judged by the large changes in PCr and lactate contents. PCr was slightly but significantly higher in BTS-treated muscles (Table 4), but the depletion of PCr after stimulation was virtually complete in both groups. As shown during the 10-s tetanus, the decrease of ATP observed during control was attenuated by BTS. The difference in ATP between BTS and control was also observed when repeated tetani were performed in the absence of NaCN (data not shown). Thus substantial decreases in ATP occurred only when cross bridges were active and limiting levels of PCr were reached (25 µmol/g dry wt).
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lactate). ATP turnover averaged 261 and 195 µmol/g dry wt in control and BTS, respectively, and, hence, cross bridges accounted for only 25% of the total ATP consumption during repeated tetani. Thus the differential effects of BTS on ATP turnover and force x time integral during repeated tetani were in agreement with those observed during continuous tetani (Fig. 5). Of note, recent studies (8) used BTS to examine the role of actomyosin interactions during repeated contractions in activation of mitogen-activated protein kinases in isolated mouse EDL muscle. It was assumed that BTS resulted in substantial decreases in the rates of ATP consumption. The present results indicate that this assumption may not be justified. |
DISCUSSION |
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20% of total ATP consumption during isometric contraction; and 2) the rate of ATP consumption decreases as the duration of contraction increases and this occurs both in the absence and presence of BTS.
Actomyosin and SR ATP consumption.
Under all conditions studied at 30°C, cross bridges accounted for only 20% of total ATP consumption during isometric contractions. Inherent in this conclusion is the assumption that 1) mitochondrial ATP production was fully suppressed by NaCN, and 2) BTS inhibited myosin ATPase to the extent that it inhibited force and that it did not affect other energy-consuming processes. That mitochondrial ATP production was abolished by NaCN in the present study is suggested by earlier findings in isolated muscle preparations (21, 28, 45). Moreover, NaCN abolished the contraction-mediated increase in malate, a marker of oxidative metabolism, in the present study.
While other studies (5) have addressed the issue of BTS specificity on purified enzymes, potential nonspecific effects always remain a concern when working with intact muscle preparations. It has previously been shown that BTS inhibits actin-activated purified myosin ATPase with an IC50 of 3–5 µM (5, 35). Moreover, in skinned muscle fibers, BTS inhibited force and actomyosin ATPase activity to similar extents and in the presence of 25 µM BTS virtually all force and actomyosin ATPase activity were abolished (<5% of control) (46). Therefore, one may conclude that because force production was inhibited by 95% in the EDL muscle, actomyosin ATPase was inhibited to a similar extent.
The other major ATP consuming enzymes in contracting skeletal muscle are considered to be SR Ca2+-ATPase and Na+-K+-ATPase (12, 23). In intact frog skeletal muscle fibers, BTS abolished twitch force but had no effect on the shape of the Ca2+ transient (5). Other studies (3, 29) have also demonstrated that BTS does not affect the shape of Ca2+ transients in intact rat and mouse fast-twitch muscle fibers during isometric tetanic contractions. Furthermore, 25 µM BTS had no effect on SR Ca2+-ATPase activity in skinned muscle fibers (46). These data suggest that BTS did not affect Ca2+ release or uptake by the SR in the present study. The extent to which BTS may affect Na+-K+-ATPase is not clear. At 
100 µM BTS, the refractory period for repetitive stimulation was lengthened in frog muscle fibers, indicating action potential prolongation (5), which may indicate a potential effect on Na+-K+-ATPase activity. Considering that we used only 25 µM BTS and that force did not decrease during the continuous tetani in BTS-treated muscles, it appears unlikely that BTS affected Na+-K+-ATPase activity to any significant extent under the conditions studied.
Our current estimate that cross bridges account for only 20% of the total ATP utilization should be considered with respect to three factors: 1) stimulation frequency, 2) temperature, and 3) species. With regard to stimulation frequency, at 50 Hz (30°C), EDL muscle is producing only 35% of maximal tetanic force. Studies on skinned muscle fibers have demonstrated that the relative contribution of cross bridges to total ATP consumption decreases markedly as the relative force decreases (37). For example, at maximal force, cross bridges account for 75% of total ATP consumption, whereas at 35% and 10% of maximal force, the cross-bridge component decreases to 45% and 25%, respectively (37). Thus the current findings on intact muscle are in good agreement with results from skinned fibers.
With respect to temperature, most studies that have estimated cross-bridge-dependent and -independent ATP consuming components have been performed at 5–20°C. In this temperature range, the relative ATP consumption of SR Ca2+ pumps increases from 28% at 5°C to 48% at 20°C in skinned fibers (37). With the use of other techniques, Rall (30) estimated that SR Ca2+-ATPase activity increases in this temperature range, accounting for 56% of total energy liberation at 20°C. Thus temperature could also contribute to the low relative cross-bridge ATP utilization at 30°C in the present study.
With respect to species, most earlier studies that estimated cross-bridge-dependent ATP consumption were performed on frog muscle, although studies on fish, chicken, mice, and rats have also been performed (2, 7, 25, 31, 41, 42). Interestingly, recent studies (38) of fast-twitch (IIA/B and IIB) skinned human muscle fibers (at 20°C) demonstrated that cross bridges accounted for only 35–41% of total ATP consumption, whereas SR Ca2+ pumping accounted for 52–55%. Indeed estimates for SR Ca2+ pump ATP utilization as high as 70% of total (at 20°C) have been reported in skinned mammalian fast- twitch muscle preparations (22). It has also been demonstrated that free myoplasmic [Ca2+] declines much faster at the end of a tetanic contraction in mouse fast-twitch muscle fibers than in frog fast-twitch fibers, indicating faster SR Ca2+ pumping in the former (44). These data indicate that fast-twitch mammalian fibers exhibit higher rates of SR Ca2+ pumping than amphibian muscles, especially at high temperatures.
The implication from the present findings then is that ion pumping accounts for most (80%) of the energy consumption during submaximal isometric contraction in mouse fast-twitch muscle at 30°C. Assuming that SR Ca2+-ATPase is primarily responsible for the non-cross-bridge-dependent energy consumption during contraction (42), we calculate that the SR Ca2+ pumps consumed 10.7 mM ATP/s during the 2-s tetanus in the presence of BTS at 30°C (Table 3). Data from skinned fibers show that SR Ca2+ pumping is near maximal (90%) already at 35% of maximal force (37). The value of 10.7 mM ATP/s can be compared with estimates derived under comparable conditions for intact mouse fast-twitch fibers, where it was calculated that SR Ca2+ uptake occurred at a rate of 8.7 mM Ca2+/s at 22°C at a myoplasmic [Ca2+] of 1 µM (44). Assuming a Q10 of 3.1 for SR Ca2+-ATPase and 1 ATP hydrolyzed per 2 Ca2+ pumped (37), one calculates a value of 10.8 mM ATP/s at 30°C, which is in good agreement with the results of the present study.
Thus, the results demonstrate that during continuous contractions, cross bridges account for only a small fraction of the total ATP consumption, suggesting that ion pumps are the major consumers of ATP. The relatively low rate of cross-bridge ATP consumption is likely explained by the low stimulation frequency. Possibly, the high temperature and the use of mammalian muscle also contributed to the relatively low rate of cross-bridge ATP consumption.
Considering that at 50 Hz (35% of maximal force), cross bridges accounted for 20% of total ATP consumption, it might seem surprising that during repeated tetani at 70 Hz (60% of maximal force) the cross-bridge component was not >25%. One should recall, however, that during repeated tetani, part of the SR Ca2+ pump ATP utilization also occurs during the recovery period between tetani. Therefore, the relative contribution of cross bridges to total ATP utilization during the force-generating phase is >25%.
ATP turnover during continuous contraction. It is well established that at the onset of contraction, fast-twitch fibers exhibit a high ATP turnover rate that decreases with time although force is maintained fairly constant (6, 7, 10, 15, 42). Similar results were obtained in the present study at higher temperature and lower relative forces. Traditionally, the decrease in the ATP turnover rate has been attributed to decreases in the activity of actomyosin ATPase (6). However, in the present study, the same phenomenon was observed in muscles treated with BTS. Of note, one study (43) estimated that after continuous tetani in mouse fast-twitch muscle fibers (22°C), SR Ca2+ uptake decreases by >50% after a 1-s tetanus compared with a 0.1-s tetanus. Accordingly, our data indicate that both cross-bridge cycling and SR Ca2+ pumping decreased by the same relative extent during continuous tetani. However, because the SR Ca2+ pumps were the major ATP consumers during the contractions, we suggest that the large decrease in the ATP turnover rate was primarily a consequence of a decrease in ATP utilization by the SR Ca2+ pumps in both control and BTS-treated muscles.
In conclusion, these data demonstrate that cross bridges (i.e., actomyosin ATPase) consume only 20% of the total ATP consumption during contraction in mouse fast-twitch skeletal muscle under near-physiological conditions, suggesting that ion pumping is the major energy-consuming process.
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FOOTNOTES |
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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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REFERENCES |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
|---|
2. Barclay CJ, Curtin NA, and Woledge RC. Changes in crossbridge and non-cross-bridge energetics during moderate fatigue of frog muscle fibres. J Physiol 468: 543–555, 1993.
3. Bruton JD, Pinniger GJ, Lannergren J, and Westerblad H. The effects of the myosin-II inhibitor N-benzyl-p-toluene sulphonamide (BTS) on the development of muscle fatigue in mouse single intact toe muscle fibres. Acta Physiol 186: 59–65, 2006.[CrossRef]
4. Byron KL, Puglisi JL, Holda JR, Eble D, and Samarel AM. Myosin heavy chain turnover in cultured neonatal rat heart cells: effects of [Ca2+]i and contractile activity. Am J Physiol Cell Physiol 271: C1447–C1456, 1996.
5. Cheung A, Dantzig JA, Hollingworth S, Baylor SM, Goldman YE, Mitchison TJ, and Straight AF. A small-molecule inhibitor of skeletal muscle myosin II. Nat Cell Biol 4: 83–88, 2002.[CrossRef][ISI][Medline]
6. Crow MT and Kushmerick MJ. Chemical energetics of slow- and fast-twitch muscles of the mouse. J Gen Physiol 79: 147–166, 1982.
7. Crow MT and Kushmerick MJ. Correlated reduction of velocity of shortening and the rate of energy utilization in mouse fast-twitch muscle during a continuous tetanus. J Gen Physiol 82: 703–720, 1983.
8. Dentel JN, Blanchard SG, Ankrapp DP, McCabe LR, and Wiseman RW. Inhibition of cross-bridge formation has no effect on contraction-associated phosphorylation of p38 MAPK in mouse skeletal muscle. Am J Physiol Cell Physiol 288: C824–C830, 2005.
9. Fryer MW, Neering IR, and Stephenson DG. Effects of 2,3-butanedione monoxime on the contractile activation properties of fast- and slow-twitch rat muscle fibres. J Physiol 407: 53–75, 1988.
10. He ZH, Bottinelli R, Pellegrino MA, Ferenczi MA, and Reggiani C. ATP consumption and efficiency of human single muscle fibers with different myosin isoform composition. Biophys J 79: 945–961, 2000.
11. Hennig R and Lomo T. Firing patterns of motor units in normal rats. Nature 314: 164–166, 1985.[CrossRef][Medline]
12. Homsher E. Muscle enthalpy production and its relationship to actomyosin ATPase. Annu Rev Physiol 49: 673–690, 1987.[CrossRef][ISI][Medline]
13. Homsher E, Lacktis J, Yamada T, and Zohman G. Repriming and reversal of the isometric unexplained enthalpy in frog skeletal muscle. J Physiol 393: 157–170, 1987.
14. Homsher E, Mommaerts WF, Ricchiuti NV, and Wallner A. Activation heat, activation metabolism and tension-related heat in frog semitendinosus muscles. J Physiol 220: 601–625, 1972.
15. Homsher E, Rall JA, Wallner A, and Ricchiuti NV. Energy liberation and chemical change in frog skeletal muscle during single isometric tetanic contractions. J Gen Physiol 65: 1–21, 1975.
16. Horiuti K, Higuchi H, Umazume Y, Konishi M, Okazaki O, and Kurihara S. Mechanism of action of 2,3-butanedione 2-monoxime on contraction of frog skeletal muscle fibres. J Muscle Res Cell Motil 9: 156–164, 1988.[CrossRef][ISI][Medline]
17. Ivy JL, Chi MM, Hintz CS, Sherman WM, Hellendall RP, and Lowry OH. Progressive metabolite changes in individual human muscle fibers with increasing work rates. Am J Physiol Cell Physiol 252: C630–C639, 1987.
18. Katz A. G-1,6-P2, glycolysis, and energy metabolism during circulatory occlusion in human skeletal muscle. Am J Physiol Cell Physiol 255: C140–C144, 1988.
19. Katz A, Andersson DC, Yu J, Norman B, Sandstrom ME, Wieringa B, and Westerblad H. Contraction-mediated glycogenolysis in mouse skeletal muscle lacking creatine kinase: the role of phosphorylase b activation. J Physiol 553: 523–531, 2003.
20. Katz A, Sahlin K, and Henriksson J. Muscle ATP turnover rate during isometric contraction in humans. J Appl Physiol 60: 1839–1842, 1986.
21. Kunz WS, Kudin A, Vielhaber S, Elger CE, Attardi G, and Villani G. Flux control of cytochrome c oxidase in human skeletal muscle. J Biol Chem 275: 27741–27745, 2000.
22. Kurebayashi N and Ogawa Y. Discrimination of Ca2+-ATPase activity of the sarcoplasmic reticulum from actomyosin-type ATPase activity of myofibrils in skinned mammalian skeletal muscle fibres: distinct effects of cyclopiazonic acid on the two ATPase activities. J Muscle Res Cell Motil 12: 355–365, 1991.[CrossRef][ISI][Medline]
23. Kushmerick MJ. Energetics of muscle contraction. In: Handbook of Physiology. Skeletal Muscle. Bethesda, MD: Am. Physiol. Soc., 1983, sect. 10, chapt. 7, 1983, p. 189–236.
24. Lännergren J and Westerblad H. The temperature dependence of isometric contractions of single, intact fibres dissected from a mouse foot muscle. J Physiol 390: 285–293, 1987.
25. Lou F, Curtin N, and Woledge R. The energetic cost of activation of white muscle fibres from the dogfish Scyliorhinus canicula. J Exp Biol 200: 495–501, 1997.[Abstract]
26. Lowry OH and Passonneau JV. A Flexible System of Enzymatic Analysis. New York: Academic, 1972.
27. Marechal G, Coulton GR, and Beckers-Bleukx G. Mechanical power and myosin composition of soleus and extensor digitorum longus muscles of ky mice. Am J Physiol Cell Physiol 268: C513–C519, 1995.
28. Nishimura M, Awano H, Hasegawa T, Yagasaki O, and Ito K. Oxygen consumption stimulated by increases in permeability of Na+ of mouse diaphragm muscle in vitro. Gen Pharmacol 22: 539–544, 1991.[ISI][Medline]
29. Pinniger GJ, Bruton JD, Westerblad H, and Ranatunga KW. Effects of a myosin-II inhibitor (N-benzyl-p-toluene sulphonamide, BTS) on contractile characteristics of intact fast-twitch mammalian muscles fibres. J Muscle Res Cell Motil 26: 135–141, 2005.[CrossRef][ISI][Medline]
30. Rall JA. Energetics of Ca2+ cycling during skeletal muscle contraction. Fed Proc 41: 155–160, 1982.[ISI][Medline]
31. Rall JA and Schottelius BA. Energetics of contraction in phasic and tonic skeletal muscles of the chicken. J Gen Physiol 62: 303–323, 1973.
32. Ranatunga KW and Wylie SR. Temperature-dependent transitions in isometric contractions of rat muscle. J Physiol 339: 87–95, 1983.
33. Sahlin K, Edstrom L, and Sjoholm H. Fatigue and phosphocreatine depletion during carbon dioxide-induced acidosis in rat muscle. Am J Physiol Cell Physiol 245: C15–C20, 1983.
34. Sahlin K, Harris RC, and Hultman E. Resynthesis of creatine phosphate in human muscle after exercise in relation to intramuscular pH and availability of oxygen. Scand J Clin Lab Invest 39: 551–558, 1979.[ISI][Medline]
35. Shaw MA, Ostap EM, and Goldman YE. Mechanism of inhibition of skeletal muscle actomyosin by N-benzyl-p-toluenesulfonamide. Biochemistry 42: 6128–6135, 2003.[CrossRef][Medline]
36. Smith IC. Energetics of activation in frog and toad muscle. J Physiol 220: 583–599, 1972.
37. Stienen GJ, Zaremba R, and Elzinga G. ATP utilization for calcium uptake and force production in skinned muscle fibres of Xenopus laevis. J Physiol 482: 109–122, 1995.[ISI][Medline]
38. Szentesi P, Zaremba R, van Mechelen W, and Stienen GJ. ATP utilization for calcium uptake and force production in different types of human skeletal muscle fibres. J Physiol 531: 393–403, 2001.
39. Thomason DB and Booth FW. Atrophy of the soleus muscle by hindlimb unweighting. J Appl Physiol 68: 1–12, 1990.
40. Tripathy A, Xu L, Pasek DA, and Meissner G. Effects of 2,3-butanedione 2-monoxime on Ca2+ release channels (ryanodine receptors) of cardiac and skeletal muscle. J Membr Biol 169: 189–198, 1999.[CrossRef][ISI][Medline]
41. Wendt IR and Gibbs CL. Energy production of rat extensor digitorum longus muscle. Am J Physiol 224: 1081–1086, 1973.
42. West TG, Curtin NA, Ferenczi MA, He ZH, Sun YB, Irving M, and Woledge RC. Actomyosin energy turnover declines while force remains constant during isometric muscle contraction. J Physiol 555: 27–43, 2004.
43. Westerblad H and Allen DG. Relaxation, [Ca2+]i and [Mg2+]i during prolonged tetanic stimulation of intact, single fibres from mouse skeletal muscle. J Physiol 480: 31–43, 1994.[ISI][Medline]
44. Westerblad H, Lannergren J, and Allen DG. Slowed relaxation in fatigued skeletal muscle fibers of Xenopus and mouse. Contribution of [Ca2+]i and cross-bridges. J Gen Physiol 109: 385–399, 1997.
45. Wiedemann FR and Kunz WS. Oxygen dependence of flux control of cytochrome c oxidase: implications for mitochondrial diseases. FEBS Lett 422: 33–35, 1998.[CrossRef][ISI][Medline]
46. Young IS, Harwood CL, and Rome LC. Cross-bridge blocker BTS permits direct measurement of SR Ca2+ pump ATP utilization in toadfish swimbladder muscle fibers. Am J Physiol Cell Physiol 285: C781–C787, 2003.
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) and after (
) 60-min exposure to 25 µM BTS. Data for the contralateral mouse EDL (B), mouse soleus (D), and rat soleus (F) muscles, respectively, are shown before (
