Evidence for Unique Structural Change of Thin Filaments upon Calcium Activation of Insect Flight Muscle

Iwamoto, Hiroyuki

doi:10.1016/j.jmb.2009.05.002

Cited by 25 publications

(54 citation statements)

References 44 publications

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“…On this basis, it appears that there were no gross shifts in Ca 2+ sensitivity with temperature of the contractile filaments within this large range of Ca 2+ concentrations. Our observations do, to some extent, contrast earlier findings on locust flight muscle, where binding of Ca 2+ to troponin was found to be compromised at low temperature, resulting in lower force production (Iwamoto, 2009). We cannot exclude the possibility that low temperature shifts Ca 2+ sensitivity in the range of concentrations beyond those examined here.…”

Section: Thermal Sensitivity Of Isometric Force Production and Contracontrasting

confidence: 99%

“…For example, in muscles of larval Drosophila, the L-type Ca 2+ current that is responsible for the AP upstroke and Ca 2+ release from internal stores has slower kinetics and markedly reduced amplitude at low temperature (Frolov and Singh, 2013). Additionally, the isometric force production of the contractile proteins is reduced in several insect species at low temperature (Orentlicher et al, 1977;Godt and Lindley, 1982;Iwamoto, 2009). On the basis of these sporadic findings, it is, however, still difficult to determine how E-C coupling fails at low temperature in insect muscle because none of the studies have systematically explored all steps in E-C coupling in one particular insect species.…”

Section: +mentioning

confidence: 99%

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Reduced L-type Ca2+ current and compromised excitability induce loss of skeletal muscle function during acute cooling in locust

Findsen

Overgaard

Pedersen

2016

Journal of Experimental Biology

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Low temperature causes most insects to enter a state of neuromuscular paralysis, termed chill coma. The susceptibility of insect species to chill coma is tightly correlated to their distribution limits and for this reason it is important to understand the cellular processes that underlie chill coma. It is known that muscle function is markedly depressed at low temperature and this suggests that chill coma is partly caused by impairment in the muscle per se. To find the cellular mechanism(s) underlying muscle dysfunction at low temperature, we examined the effect of low temperature (5°C) on several events in excitation-contraction coupling in the migratory locust (Locusta migratoria). Intracellular membrane potential recordings during single nerve stimulations showed that 70% of fibers at 20°C produced an action potential (AP), while only 55% of fibers were able to fire an AP at 5°C. Reduced excitability at low temperature was caused by an ∼80% drop in L-type Ca 2+ current and a depolarizing shift in its activation of around 20 mV, which means that a larger endplate potential would be needed to activate the muscle AP at low temperature. In accordance, we showed that intracellular Ca 2+ transients were largely absent at low temperature following nerve stimulation. In contrast, maximum contractile force was unaffected by low temperature in chemically skinned muscle bundles, which demonstrates that the function of the contractile filaments is preserved at low temperature. These findings demonstrate that reduced L-type Ca 2+ current is likely to be the most important factor contributing to loss of muscle function at low temperature in locust.

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Section: Thermal Sensitivity Of Isometric Force Production and Contracontrasting

confidence: 99%

Section: +mentioning

confidence: 99%

Reduced L-type Ca2+ current and compromised excitability induce loss of skeletal muscle function during acute cooling in locust

Findsen

Overgaard

Pedersen

2016

Journal of Experimental Biology

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“…Here, the weaker intensity change of the second ALL of mutated cells set at a full thin-thick filament overlap proves that tropomyosin displacement over the surface of actin is partially hindered when compared with controls. In an attempt to identify the origin of such dysfunction (calcium-vs. myosin-related), fibers were overstretched to minimize thin-thick filament overlap (18). Upon addition of calcium, the second ALL intensity change of mutated cells was also smaller when compared with control fibers, demonstrating that calcium-and myosin-induced movements are both unspecifically altered.…”

Section: Discussionmentioning

confidence: 99%

“…Two to 3 days before X-ray recordings, fiber bundles were desucrosed and transferred to a relaxing solution, and single fibers were dissected. Arrays of ≈30 fibers were set up (17,18,29,31). Both ends of each fiber were clamped to half-split gold meshes for electron microscopy (width, 3 mm), which had been glued to precision-machined ceramic chips (width, 3 mm) designed to fit to a specimen chamber.…”

Section: Methodsmentioning

confidence: 99%

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A myopathy-linked tropomyosin mutation severely alters thin filament conformational changes during activation

Ochala

Iwamoto

Larsson

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Human point mutations in β-and γ-tropomyosin induce contractile deregulation, skeletal muscle weakness, and congenital myopathies. The aim of the present study was to elucidate the hitherto unknown underlying molecular mechanisms. Hence, we recorded and analyzed the X-ray diffraction patterns of human membranepermeabilized muscle cells expressing a particular β-tropomyosin mutation (R133W) associated with a loss in cell force production, in vivo muscle weakness, and distal arthrogryposis. Upon addition of calcium, we notably observed less intensified changes, compared with controls, (i) in the second (1/19 nm ) actin layer lines of cells set at a sarcomere length, allowing an optimal thin-thick filament overlap; and (ii) in the second actin layer line of overstretched cells. Collectively, these results directly prove that during activation, switching of a positive to a neutral charge at position 133 in the protein partially hinders both calcium-and myosin-induced tropomyosin movement over the thin filament, blocking actin conformational changes and consequently decreasing the number of cross-bridges and subsequent force production.actin | cross-bridge | single-muscle fiber | X-ray diffraction T ropomyosin is expressed in multiple isoforms in most mammalian cell types (1, 2). The isoform diversity is related to alternative splicing, alternative promoters, and differential RNA processing, resulting in specific striated muscle, smooth muscle, and nonmuscle isoforms (2). In skeletal muscle there are three major isoforms, α, β, and γ, which are encoded by the TPM1, TPM2, and TPM3 genes, respectively (2). A number of missense defects in these TPM2 and TPM3 genes cause single amino acid changes in β-and γ-tropomyosin, skeletal muscle weakness, and myopathies (3). The molecular mechanisms by which such subtle defects result in muscle contractile dysfunction remain unclear and need to be elucidated with the aim of targeting potential therapies.A unique β-tropomyosin mutation (R133W) resulting from a defect in the TPM2 gene was recently identified in patients with distal arthrogryposis and an autosomal dominant congenital myopathy (4). These patients suffered from generalized weakness in both proximal and distal muscles. Biopsy specimens did not reveal any signs of atrophy or other histopathological abnormalities (4). Nevertheless, in normal-sized fibers, cell-physiological experiments disclosed a large decrease in maximal isometric force production ( Fig. 1) as well as changes in kinetics: that is, a slower rate of force development and a faster maximum unloaded shortening velocity (5), implying a slower rate of motor protein myosin attachment and a faster rate of detachment from actin monomers. This finding suggests a reduced number of cross-bridges in the strong binding state, resulting in overall weakness in the patients (5). How does the R133W mutation induce such dysfunction? To date, at the molecular level no experimentally-based explanation exists.In skeletal muscle, tropomyosin is an integral component of the sar...

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Myofilament lattice structure in presence of a skeletal myopathy-related tropomyosin mutation

Ochala

Iwamoto

2013

J Muscle Res Cell Motil

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Human tropomyosin mutations deregulate skeletal muscle contraction at the cellular level. One key feature is the slowing of the kinetics of force development. The aim of the present study was to characterize the potential underlying molecular mechanisms by recording and analyzing the X-ray diffraction patterns of human membrane-permeabilized muscle cells expressing a particular β-tropomyosin mutation (E41K). During resting conditions, the d1,0 lattice spacing, Δ1,0 and I1,1 to I1,0 ratio were not different from control values. These results suggest that, in presence of the E41K β-tropomyosin mutation, the myofilament lattice geometry is well maintained and therefore may not have any detrimental influence on the contraction mechanisms and thus, on the rate of force generation.

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Evidence for Unique Structural Change of Thin Filaments upon Calcium Activation of Insect Flight Muscle

Cited by 25 publications

References 44 publications

Reduced L-type Ca2+ current and compromised excitability induce loss of skeletal muscle function during acute cooling in locust

Reduced L-type Ca2+ current and compromised excitability induce loss of skeletal muscle function during acute cooling in locust

A myopathy-linked tropomyosin mutation severely alters thin filament conformational changes during activation

Myofilament lattice structure in presence of a skeletal myopathy-related tropomyosin mutation

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