Administration of a creatine analogue induces isomyosin transitions in muscle

Moerland, Timothy S.; Wolf, Nurit; Kushmerick, Martin J.

doi:10.1152/ajpcell.1989.257.4.c810

Cited by 59 publications

(39 citation statements)

References 24 publications

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“…The mechanism underlying the lower Vmax in CK[ -/ -] Dia may relate in p a rt to th e alteration in MHC phenotype of the Dia in response to combined CK-M and ScCKmit deficiency, i.e., an increased MHCsi0W and diminished MHC2B expression. This shift in MHC isoform expression, also observed in p-GPA-treated animals (19), m ight be expected to decrease the overall actomyosin ATPase activity of the CK[-/-] Dia, as well as cross-bridge cycling ra te and y max-However, the difference in MHC isoform expression between Ctl and C K [-/-] Dia was relatively small and, therefore, unlikely to fully ac count for th e difference in Vmax. Other possible contrib uting factors to th e difference in Vmax between Ctl and CK[-/ -] Dia include alterations in regulatory contrac tile protein isoforms, i.e., alkaline myosin light chain composition (5) and troponin.…”

Section: Discussionsupporting

confidence: 63%

Combined myofibrillar and mitochondrial creatine kinase deficiency impairs mouse diaphragm isotonic function

Watchko

Daood

Sieck³

et al. 1997

Journal of Applied Physiology

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atine kinase deficiency impairs mouse diaphragm isotonic function. J. Appl. Physiol. 82(5): 1416-1423,1997.-Creatine kinase (CK) is an enzyme central to cellular high-energy phosphate metabolism in muscle. To characterize the physi ological role of CK in respiratory muscle during dynamic contractions, we compared the fore e-velocity relationships, power, and work output characteristics of the diaphragm (Dia) from mice with combined myofibrillar and sarcomeric mitochondrial CK deficiency (CK [-7-]) with CK-sufficient controls (Ctl). Maximum velocity of shortening was signifi cantly lower in CK[-/-] Dia (14.1 ± 0.9 L Js7 where L0 is optimal fiber length) compared with Ctl Dia (17.5 ± 1.1 LJs) (P < 0.01). Maximum power was obtained at 0.4-0.5 tetanic force in both groups; absolute maximum power (2,293 ± 138 W/m2) and work (201 ± 9 J/m2) were lower in CK[-/ -] Dia compared with Ctl Dia (2,744 ± 146 W/m2 and 284 ± 26 J/m2, respectively) (P < 0.05). The ability of CK [-/-] Dia to sustain shortening during repetitive isotonic activation (75 Hz, 330-ms duration repeated each second at 0.4 tetanic force load) was markedly impaired, with CK[-/-] Dia power and work declining to zero by 37 ± 4 s, compared with 61 ± 5 s in Ctl Dia. We conclude that combined myofibrillar and sarcomeric mitochondrial CK deficiency profoundly impairs Dia power and work output, underscoring the functional importance of CK during dynamic contractions in skeletal muscle. respiratory muscle; fatigue; myosin heavy chain r e s p i r a t o r y MUSCLE FATIGUE is a phenom enon of clini cal im portance contributing to the development of ventilatory failure in neonates and adults. The factors predisposing muscle to fatigue are felt prim arily to resu lt from an im balance betw een energy supply and dem and (25, 35). The accum ulation of energy m etabo lites in all probability also plays an im portant role (1,6,8). A lteration of th e capacity of skeletal muscle to produce or sustain ATP levels is th u s likely to affect muscle fatigue resistance. C reatine kinase (CK), an enzyme central to cellular high-energy phosphate m e tabolism in muscle, m ay be im p o rtan t in this regard. CK catalyzes the following reaction PC r +MgAJDP-+ H + <=> Cr + MgATP2" where PC r is phosphocreatine and Cr is creatine. The high level of CK activity found in skeletal muscle ensures th at, w hen consistent high-energy phosphate production is necessary during repetitive contractile activity, ATP levels will be m aintained at the expense of PCr. This role of CK as an ATP buffer is widely accepted (18, 33).Defining a physiological role for CK in skeletal muscle fatigue, however, has been difficult, with prior studies using substrate analogs (10,16,17,20) of Cr to assess the functional consequences of impaired CK activity. These studies have generated disparate re sults and exclusively examined fatigue under repetitive isometric conditions. The respiratory muscles' capacity to sustain ventilation, however, is determined in large p a rt by its ability to shorten and m aintain for...

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Section: Discussionsupporting

confidence: 63%

Combined myofibrillar and mitochondrial creatine kinase deficiency impairs mouse diaphragm isotonic function

Watchko

Daood

Sieck³

et al. 1997

Journal of Applied Physiology

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“…They related their findings to the more cost-efficient myosins present in these β-GPA treated muscles [15] and concluded that the observed myosin shift led to a twofold increase in contractile economy. Based on these findings and a similar MyHC type IIa/IIb ratio, increase of 119 and 116% in CK-deficient and β-GPA treated fast-twitch EDL muscles [15,22], respectively, we expected to, likewise, find a twofold increased contractile economy in MiM-CK −/− EDL muscle. This hypothesis was tested.…”

Section: Discussionmentioning

confidence: 98%

“…In muscle lacking a fully functional CK system, either due to β-GPA feeding [7,[15][16][17] or by deletion of CK enzymes [2,18], a shift to slower MyHC isoforms (type I and IIa increase) has been observed in fast-twitch gastrocnemius and EDL muscles. The energetic cost to maintain tension is known to depend on the myosin isoform composition due to intrinsic differences in the cross-bridge cycle rates and the myosin ATPase activities [14,19,20].…”

Section: Discussionmentioning

confidence: 99%

“…Moerland et al studied the contractile economy based on the poststimulatory oxygen consumption during recovery in EDL and SOL muscles of β-GPA fed mice and observed a 50% decrease in energetic cost to maintain tetanus tension in both muscle types [8]. They related their findings to the more cost-efficient myosins present in these β-GPA treated muscles [15] and concluded that the observed myosin shift led to a twofold increase in contractile economy. Based on these findings and a similar MyHC type IIa/IIb ratio, increase of 119 and 116% in CK-deficient and β-GPA treated fast-twitch EDL muscles [15,22], respectively, we expected to, likewise, find a twofold increased contractile economy in MiM-CK −/− EDL muscle.…”

Section: Discussionmentioning

confidence: 99%

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Increased resistance to fatigue in creatine kinase deficient muscle is not due to improved contractile economy

Veld

Nicolay

Jeneson

2006

Pflugers Arch - Eur J Physiol

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There has been speculation on the origin of the increased endurance of skeletal muscles in creatine kinase (CK)-deficient mice. Important factors that have been raised include the documented increased mitochondrial capacity and alterations in myosin heavy chain (MyHC) isoform composition in CK-deficient muscle. More recently, the absence of inorganic phosphate release from phosphocreatine hydrolysis in exercising CK-deficient muscle has been postulated to contribute to the lower fatigueability in skeletal muscle. In this study, we tested the hypothesis that the reported shift in MyHC composition to slower isoforms in CK-deficient muscle leads to a decrease in oxygen cost of twitch performance. To that aim, extensor digitorum longus (EDL) and soleus (SOL) muscles were isolated from wild-type (WT) and knock-out mice deficient in the cytoplasmic muscle-type and sarcomeric mitochondrial isoenzymes of CK, and oxygen consumption per twitch time-tension-integral (TTI) was measured. The results show that the adaptive response to loss of CK function does not involve any major change to contractile economy of skeletal muscle.

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“…Their study shows that contraction-coupling costs per time-tension integral decline by half at longer stimulus trains in mouse extensor digitorum longus (EDL) muscle. The EDL has substantial levels of parvalbumin (Moerland et al, 1989), which act as a Ca 2+ buffer in the muscle cell. In contrast, mouse soleus muscle lacks parvalbumin and does not show a change in contraction-coupling costs under the same conditions (Moerland and Kushmerick, 1994).…”

Section: How High Is Contraction-coupling Efficiency?mentioning

confidence: 99%

High efficiency in human muscle: an anomaly and an opportunity?

Nelson

Ortega

Jubrias

et al. 2011

Journal of Experimental Biology

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SummaryCan human muscle be highly efficient in vivo? Animal muscles typically show contraction-coupling efficiencies <50% in vitro but a recent study reports that the human first dorsal interosseous (FDI) muscle of the hand has an efficiency value in vivo of 68%. We examine two key factors that could account for this apparently high efficiency value: (1) transfer of cross-bridge work into mechanical work and (2) the use of elastic energy to do external work. Our analysis supports a high contractile efficiency reflective of nearly complete transfer of muscular to mechanical work with no contribution by recycling of elastic energy to mechanical work. Our survey of reported contraction-coupling efficiency values puts the FDI value higher than typical values found in small animals in vitro but within the range of values for human muscle in vivo. These high efficiency values support recent studies that suggest lower Ca 2+ cycling costs in working contractions and a decline in cost during repeated contractions. In the end, our analysis indicates that the FDI muscle may be exceptional in having an efficiency value on the higher end of that reported for human muscle. Thus, the FDI muscle may be an exception both in contraction-coupling efficiency and in Ca 2+ cycling costs, which makes it an ideal muscle model system offering prime conditions for studying the energetics of muscle contraction in vivo.

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Administration of a creatine analogue induces isomyosin transitions in muscle

Cited by 59 publications

References 24 publications

Combined myofibrillar and mitochondrial creatine kinase deficiency impairs mouse diaphragm isotonic function

Combined myofibrillar and mitochondrial creatine kinase deficiency impairs mouse diaphragm isotonic function

Increased resistance to fatigue in creatine kinase deficient muscle is not due to improved contractile economy

High efficiency in human muscle: an anomaly and an opportunity?

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