Journal of Muscle Research and Cell Motility, Mar 1, 1999
The concentrations and diusivity of two isoforms of parvalbumin, IVa and IVb, were measured using... more The concentrations and diusivity of two isoforms of parvalbumin, IVa and IVb, were measured using quantitative SDS PAGE in single ®bers from semitendinosus muscles of the frog Rana temporaria. The concentrations of IVa and IVb were 2.9 0.3 (SEM) and 4.5 0.5 g l A1 total ®ber volume, respectively. The total concentration of parvalbumin (7.4 0.8 g l A1 total ®ber) corresponds to a cytosolic concentration of 0.9 0.1 mmol l A1 myoplasmic water. Estimates for the transverse and longitudinal diusion coecients for parvalbumin at 4°C were obtained in two ways: (1) by diusion of parvalbumin out of skinned ®bers into droplets of relaxing solution, and (2) by diusion of parvalbumin between two juxtaposed skinned ®bers under oil. The transverse diusion coecient obtained using the droplet method was signi®cantly lower than that obtained using juxtaposed ®bers, but the longitudinal diusion coecients obtained from both methods were similar. The juxtaposed ®ber method more accurately approximates parvalbumin diusion in undisturbed myoplasm because no arti®cial solutions were used and, upon ®ber-to-®ber contact, a potentially confounding oil barrier at the interface rapidly disperses. The juxtaposed ®ber method yielded values for transverse (4.27 0.87´10 A7 cm 2 s A1) and longitudinal (3.20 0.74´10 A7 cm 2 s A1) diusion coecients that were not signi®cantly dierent, suggesting that diusion of parvalbumin in myoplasm is essentially isotropic. The average diusion coecient of frog parvalbumin in myoplasm (3.74 0.81´10 A7 cm 2 s A1 ; 4°C) is approximately a third of that estimated for frog parvalbumin diusing in bulk water into and out of 3% agarose cylinders (10.6´10 A7 cm 2 s A1 ; 4°C). The reduced translational mobility of parvalbumin in myoplasm re¯ects an elevated eective viscosity due to tortuosity and viscous drag imposed by the ®xed proteins of the cytomatrix and the numerous diusible particles of the cytosol.
Background: The small amount of α-myosin heavy chain (MHC) normally present in non-failing human ... more Background: The small amount of α-myosin heavy chain (MHC) normally present in non-failing human myocardium (5–7%) is downregulated in failing myocardium to nearly undetectable levels. The physiological relevance of this small shift is uncertain, but some studies employing manipulation of thyroid state in rodents to vary MHC isoform ratio suggest that it has a significant, negative functional consequence. In order to determine the significance of small MHC isoform shifts in a preparation that is closer to human myocardium and does not require thyroid manipulation, we examined the effects of α-MHC content on myofilament function by using transgenic (TG) rabbits containing varying levels of α-MHC superimposed on a normal α-MHC background, as is present in both rabbits and humans. Methods: Papillary muscle strips were obtained from two types of TG rabbits with different α-MHC contents [5 TG rabbits with 15 % α-/85% β-MHC (TG15) and 4 TG rabbits with 40% α-/60% β-MHC (TG40)] and age-matched NTG controls containing 100% β-MHC (4 NTG15 and 4 NTG 40, respectively). Dissected strips were chemically demembranated with detergent, attached to a length motor and force gauge, and stretched to sarcomere length 2.2 μm. Myofilaments were calcium activated and small-amplitude sinusoidal length perturbation analysis was performed at 17°C over a wide range of frequencies to delineate cross-bridge kinetics. Result: Maximum isometric tension was similar in TG and NTG groups (17.6 ± 2.0 in TG15 vs 18.9 ± 2.8 in NTG15 and 26.6 ± 3.1 in TG40 vs 24.3 ± 3.7 in NTG40). ``Dip” frequency, the frequency of minimal dynamic stiffness determined during sinusoidal analysis that correlates with the rate of actomyosin cross-bridge kinetics, was higher in TG40s compared with NTG40s (0.70 ± 0.04 vs 0.39 ± 0.09 Hz, P 0.01). In contrast, there was no difference between TG15s and NTG15s in dip frequency (0.71 ± 0.09 vs 0.67 ± 0.10 Hz). Conclusion: An increased proportion of α-MHC to ~40% on a α-MHC background results in more rapid rates of cross-bridge cycling. Decreasing α-MHC content to 15% leads to undetectable differences in cross-bridge kinetics. These findings suggest that the much smaller change in α-MHC that occurs in failing human myocardium is not functionally significant.
Pflügers Archiv - European Journal of Physiology, 1981
Single skinned muscle fibers were osmotically compressed back to and below their in situ size by ... more Single skinned muscle fibers were osmotically compressed back to and below their in situ size by addition of a large, random-coil polymer (Deytran T 500; ~r N = 180,000; _~r w = 461,000) to the bathing medium. Maximal Ca z § activated tension in fibers swollen (zero Dextran, fiber width 21% above in situ) or near in situ size (5 70 Dextran, in g/100 ml final solution) was similar, but compression to 86 70 of in situ width with 10 % Dextran decreased maximal force by 15 % relative to polymer-free control. While the relative tension-pCa relation in 0 and 10 % Dextran was similar, with a pCa of 6.37 required for 5070 activation, that in 5% Dextran was more sensitive to Ca 2 +, with a pCa s 0 of 6.66. We feel these effects are most likely due to changes in interfilament spacing with compression and that alterations in Ca 2 +sensitivity might be explained by changes in cross-bridge angle or in the concomitant attachment-detachment rate constants which would be expected to influence the troponin-Ca / + binding equilibrium, as has been proposed by others.
The demembranated (skinned) muscle fiber preparation is widely used to investigate muscle contrac... more The demembranated (skinned) muscle fiber preparation is widely used to investigate muscle contraction because the intracellular ionic conditions can be precisely controlled. However, plasma membrane removal results in a loss of osmotic regulation, causing abnormal hydration of the myofilament lattice and its proteins. We investigated the structural and functional consequences of varied myofilament lattice spacing and protein hydration on cross-bridge rates of force development and detachment in Drosophila melanogaster indirect flight muscle, using x-ray diffraction to compare the lattice spacing of dissected, osmotically compressed skinned fibers to native muscle fibers in living flies. Osmolytes of different sizes and exclusion properties (Dextran T-500 and T-10) were used to differentially alter lattice spacing and protein hydration. At in vivo lattice spacing, cross-bridge attachment time (t on) increased with higher osmotic pressures, consistent with a reduced cross-bridge detachment rate as myofilament protein hydration decreased. In contrast, in the swollen lattice, t on decreased with higher osmotic pressures. These divergent responses were reconciled using a structural model that predicts t on varies inversely with thick-to-thin filament surface distance, suggesting that cross-bridge rates of force development and detachment are modulated more by myofilament lattice geometry than protein hydration. Generalizing these findings, our results suggest that cross-bridge cycling rates slow as thick-to-thin filament surface distance decreases with sarcomere lengthening, and likewise, cross-bridge cycling rates increase during sarcomere shortening. Together, these structural changes may provide a mechanism for altering cross-bridge performance throughout a contraction-relaxation cycle.
We have developed a reverse-genetic approach to study the function of flightin, a unique protein ... more We have developed a reverse-genetic approach to study the function of flightin, a unique protein of the flight muscle myofibril of Drosophila melanogaster. We describe the generation and characterization of Df(3L)fln1, a lethal genetic deficiency in the 76BE region of the third chromosome which deletes several genes, including the gene for flightin. We show that heterozygous flies harboring the Df(3L)fln1 mutation exhibit both impaired flight and ultrastructural defects in their flight muscle myofibrils. We found that the mutation does not interfere with assembly of the myofibril but leads to disorganization of peripheral myofilaments in adult myofibrils. Most myofibrils, nevertheless, retain an intact core that represents approximately 80 % of the normal lattice diameter. Mechanical analysis of single skinned flight muscle fibers demonstrates that the mutation has no significant effect on net power output but increases the frequency at which maximum power is delivered to the wings,...
Metabolism sustains life through enzyme-catalyzed chemical reactions within the cells of all orga... more Metabolism sustains life through enzyme-catalyzed chemical reactions within the cells of all organisms. The coupling of catalytic function to the structural organization of enzymes contributes to the kinetic optimization important to tissue-specific and whole-body function. This coupling is of paramount importance in the role that muscle plays in the success of Animalia. The structure and function of glycolytic enzyme complexes in anaerobic metabolism have long been regarded as a major regulatory element necessary for muscle activity and whole-body homeostasis. While the details of this complex remain to be elucidated through in vivo studies, this review will touch on recent studies that suggest the existence of such a complex and its structure. A potential model for glycolytic complexes and related subcomplexes is introduced.
Fatigue is a common symptom of numerous acute and chronic diseases, including myalgic encephalomy... more Fatigue is a common symptom of numerous acute and chronic diseases, including myalgic encephalomyelitis/chronic fatigue syndrome, multiple sclerosis, heart failure, cancer, and many others. In these multi-system diseases the physiological determinants of enhanced fatigue encompass a combination of metabolic, neurological, and myofibrillar adaptations. Previous research studies have focused on adaptations specific to skeletal muscle and their role in fatigue. However, most have neglected the contribution of physical inactivity in assessing disease syndromes, which, through deconditioning, likely contributes to symptomatic fatigue. In this commentary, we briefly review disease-related muscle phenotypes in the context of whether they relate to the primary disease or whether they develop secondary to reduced physical activity. Knowledge of the etiology of the skeletal muscle adaptations in these conditions and their contribution to fatigue symptoms is important for understanding the utility of exercise rehabilitation as an intervention to alleviate the physiological precipitants of fatigue.
Advances in experimental medicine and biology, 2005
Table 1 summarizes the primary mechanisms most likely responsible for modifying wing beat frequen... more Table 1 summarizes the primary mechanisms most likely responsible for modifying wing beat frequency (WBF) and muscle power in the Drosophila mutants discussed above. The different outcomes reflect different mechanisms that come into play, depending on the protein and site of the mutation. For example, the reduced muscle power and WBF of the RLC phosphorylation site mutant Mlc2(S6sA,S67A) reflect the reduced number of myosin heads available to form working cross-bridges and the concomitant reduction in muscle stiffness. The mixed results of the other mutants are more difficult to explain. For example, while the reduced muscle stiffness of the paramyosin rod mutant pm(S18A) and the projectin mutant bent(D)/+ may in part reflect mutation-related increases in compliance of the thick filaments (pm(S18A)) or connecting filaments (bent(D)/+), the elevated WBF is unexpected because one would expect reduced muscle stiffness to lower WBF rather than raise it. Other aspects of the results are ...
Advances in experimental medicine and biology, 2003
... Douglas M. Swank and David W. Maughan ... Because these rates are expressed as a stUn (2Jtb +... more ... Douglas M. Swank and David W. Maughan ... Because these rates are expressed as a stUn (2Jtb + 2m;) and product (21th x 21tc) in the transient solutions of the cross-bridge schemes presented below, we plotted both stUn and product as functions of [Pi], following the method of ...
Journal of muscle research and cell motility, 2001
The similarity of amino acid sequence and motifs of the N-terminal extensions of certain class II... more The similarity of amino acid sequence and motifs of the N-terminal extensions of certain class II myosin light chains, found throughout the animal kingdom, suggest a common functional role. One possible role of the N-terminal extension is to enhance oscillatory work and power production in striated muscles that normally operate in an oscillatory mode. We conducted small-angle X-ray diffraction experiments and small-length-perturbation analysis to examine the structural and functional consequences of deleting the N-terminal extension of the myosin regulatory light chain (RLC) in Drosophila flight muscle. The in vivo lattice spacing of dorsal longitudinal muscle (DLM) of flies lacking the RLC N-terminal extension (Dmlc2delta2-46) was approximately 1 nm less than that of wild type (48.56 +/- 0.02 nm). The myofilament lattice of detergent-treated, demembranated DLM swelled, with the DmlcdeltaA2-46 lattice expanding more than wild type and requiring roughly twice the concentration of Dex...
American journal of physiology. Heart and circulatory physiology, 2001
The role of altered cross-bridge kinetics during the transition from cardiac hypertrophy to failu... more The role of altered cross-bridge kinetics during the transition from cardiac hypertrophy to failure is poorly defined. We examined this in Dahl salt-sensitive (DS) rats, which develop hypertrophy and failure when fed a high-salt diet (HS). DS rats fed a low-salt diet were controls. Serial echocardiography disclosed compensated hypertrophy at 6 wk of HS, followed by progressive dilatation and impaired function. Mechanical properties of skinned left ventricular papillary muscle strips were analyzed at 6 wk of HS and then during failure (12 wk HS) by applying small amplitude (0.125%) length perturbations over a range of calcium concentrations. No differences in isometric tension-calcium relations or cross-bridge cycling kinetics or mechanical function were found at 6 wk. In contrast, 12 wk HS strips exhibited increased calcium sensitivity of isometric tension, decreased frequency of minimal dynamic stiffness, and a decreased range of frequencies over which cross bridges produce work an...
News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society, 1999
Substituting an alanine for serine in the regulatory subunit of the motor protein myosin dramatic... more Substituting an alanine for serine in the regulatory subunit of the motor protein myosin dramatically alters Drosophila's flight ability. Power output, at all levels of the flight system, is reduced. This example of deciphering a protein's function by producing malfunctions illustrates the broadening use of molecular genetics in integrative biology.
Journal of Muscle Research and Cell Motility, Mar 1, 1999
The concentrations and diusivity of two isoforms of parvalbumin, IVa and IVb, were measured using... more The concentrations and diusivity of two isoforms of parvalbumin, IVa and IVb, were measured using quantitative SDS PAGE in single ®bers from semitendinosus muscles of the frog Rana temporaria. The concentrations of IVa and IVb were 2.9 0.3 (SEM) and 4.5 0.5 g l A1 total ®ber volume, respectively. The total concentration of parvalbumin (7.4 0.8 g l A1 total ®ber) corresponds to a cytosolic concentration of 0.9 0.1 mmol l A1 myoplasmic water. Estimates for the transverse and longitudinal diusion coecients for parvalbumin at 4°C were obtained in two ways: (1) by diusion of parvalbumin out of skinned ®bers into droplets of relaxing solution, and (2) by diusion of parvalbumin between two juxtaposed skinned ®bers under oil. The transverse diusion coecient obtained using the droplet method was signi®cantly lower than that obtained using juxtaposed ®bers, but the longitudinal diusion coecients obtained from both methods were similar. The juxtaposed ®ber method more accurately approximates parvalbumin diusion in undisturbed myoplasm because no arti®cial solutions were used and, upon ®ber-to-®ber contact, a potentially confounding oil barrier at the interface rapidly disperses. The juxtaposed ®ber method yielded values for transverse (4.27 0.87´10 A7 cm 2 s A1) and longitudinal (3.20 0.74´10 A7 cm 2 s A1) diusion coecients that were not signi®cantly dierent, suggesting that diusion of parvalbumin in myoplasm is essentially isotropic. The average diusion coecient of frog parvalbumin in myoplasm (3.74 0.81´10 A7 cm 2 s A1 ; 4°C) is approximately a third of that estimated for frog parvalbumin diusing in bulk water into and out of 3% agarose cylinders (10.6´10 A7 cm 2 s A1 ; 4°C). The reduced translational mobility of parvalbumin in myoplasm re¯ects an elevated eective viscosity due to tortuosity and viscous drag imposed by the ®xed proteins of the cytomatrix and the numerous diusible particles of the cytosol.
Background: The small amount of α-myosin heavy chain (MHC) normally present in non-failing human ... more Background: The small amount of α-myosin heavy chain (MHC) normally present in non-failing human myocardium (5–7%) is downregulated in failing myocardium to nearly undetectable levels. The physiological relevance of this small shift is uncertain, but some studies employing manipulation of thyroid state in rodents to vary MHC isoform ratio suggest that it has a significant, negative functional consequence. In order to determine the significance of small MHC isoform shifts in a preparation that is closer to human myocardium and does not require thyroid manipulation, we examined the effects of α-MHC content on myofilament function by using transgenic (TG) rabbits containing varying levels of α-MHC superimposed on a normal α-MHC background, as is present in both rabbits and humans. Methods: Papillary muscle strips were obtained from two types of TG rabbits with different α-MHC contents [5 TG rabbits with 15 % α-/85% β-MHC (TG15) and 4 TG rabbits with 40% α-/60% β-MHC (TG40)] and age-matched NTG controls containing 100% β-MHC (4 NTG15 and 4 NTG 40, respectively). Dissected strips were chemically demembranated with detergent, attached to a length motor and force gauge, and stretched to sarcomere length 2.2 μm. Myofilaments were calcium activated and small-amplitude sinusoidal length perturbation analysis was performed at 17°C over a wide range of frequencies to delineate cross-bridge kinetics. Result: Maximum isometric tension was similar in TG and NTG groups (17.6 ± 2.0 in TG15 vs 18.9 ± 2.8 in NTG15 and 26.6 ± 3.1 in TG40 vs 24.3 ± 3.7 in NTG40). ``Dip” frequency, the frequency of minimal dynamic stiffness determined during sinusoidal analysis that correlates with the rate of actomyosin cross-bridge kinetics, was higher in TG40s compared with NTG40s (0.70 ± 0.04 vs 0.39 ± 0.09 Hz, P 0.01). In contrast, there was no difference between TG15s and NTG15s in dip frequency (0.71 ± 0.09 vs 0.67 ± 0.10 Hz). Conclusion: An increased proportion of α-MHC to ~40% on a α-MHC background results in more rapid rates of cross-bridge cycling. Decreasing α-MHC content to 15% leads to undetectable differences in cross-bridge kinetics. These findings suggest that the much smaller change in α-MHC that occurs in failing human myocardium is not functionally significant.
Pflügers Archiv - European Journal of Physiology, 1981
Single skinned muscle fibers were osmotically compressed back to and below their in situ size by ... more Single skinned muscle fibers were osmotically compressed back to and below their in situ size by addition of a large, random-coil polymer (Deytran T 500; ~r N = 180,000; _~r w = 461,000) to the bathing medium. Maximal Ca z § activated tension in fibers swollen (zero Dextran, fiber width 21% above in situ) or near in situ size (5 70 Dextran, in g/100 ml final solution) was similar, but compression to 86 70 of in situ width with 10 % Dextran decreased maximal force by 15 % relative to polymer-free control. While the relative tension-pCa relation in 0 and 10 % Dextran was similar, with a pCa of 6.37 required for 5070 activation, that in 5% Dextran was more sensitive to Ca 2 +, with a pCa s 0 of 6.66. We feel these effects are most likely due to changes in interfilament spacing with compression and that alterations in Ca 2 +sensitivity might be explained by changes in cross-bridge angle or in the concomitant attachment-detachment rate constants which would be expected to influence the troponin-Ca / + binding equilibrium, as has been proposed by others.
The demembranated (skinned) muscle fiber preparation is widely used to investigate muscle contrac... more The demembranated (skinned) muscle fiber preparation is widely used to investigate muscle contraction because the intracellular ionic conditions can be precisely controlled. However, plasma membrane removal results in a loss of osmotic regulation, causing abnormal hydration of the myofilament lattice and its proteins. We investigated the structural and functional consequences of varied myofilament lattice spacing and protein hydration on cross-bridge rates of force development and detachment in Drosophila melanogaster indirect flight muscle, using x-ray diffraction to compare the lattice spacing of dissected, osmotically compressed skinned fibers to native muscle fibers in living flies. Osmolytes of different sizes and exclusion properties (Dextran T-500 and T-10) were used to differentially alter lattice spacing and protein hydration. At in vivo lattice spacing, cross-bridge attachment time (t on) increased with higher osmotic pressures, consistent with a reduced cross-bridge detachment rate as myofilament protein hydration decreased. In contrast, in the swollen lattice, t on decreased with higher osmotic pressures. These divergent responses were reconciled using a structural model that predicts t on varies inversely with thick-to-thin filament surface distance, suggesting that cross-bridge rates of force development and detachment are modulated more by myofilament lattice geometry than protein hydration. Generalizing these findings, our results suggest that cross-bridge cycling rates slow as thick-to-thin filament surface distance decreases with sarcomere lengthening, and likewise, cross-bridge cycling rates increase during sarcomere shortening. Together, these structural changes may provide a mechanism for altering cross-bridge performance throughout a contraction-relaxation cycle.
We have developed a reverse-genetic approach to study the function of flightin, a unique protein ... more We have developed a reverse-genetic approach to study the function of flightin, a unique protein of the flight muscle myofibril of Drosophila melanogaster. We describe the generation and characterization of Df(3L)fln1, a lethal genetic deficiency in the 76BE region of the third chromosome which deletes several genes, including the gene for flightin. We show that heterozygous flies harboring the Df(3L)fln1 mutation exhibit both impaired flight and ultrastructural defects in their flight muscle myofibrils. We found that the mutation does not interfere with assembly of the myofibril but leads to disorganization of peripheral myofilaments in adult myofibrils. Most myofibrils, nevertheless, retain an intact core that represents approximately 80 % of the normal lattice diameter. Mechanical analysis of single skinned flight muscle fibers demonstrates that the mutation has no significant effect on net power output but increases the frequency at which maximum power is delivered to the wings,...
Metabolism sustains life through enzyme-catalyzed chemical reactions within the cells of all orga... more Metabolism sustains life through enzyme-catalyzed chemical reactions within the cells of all organisms. The coupling of catalytic function to the structural organization of enzymes contributes to the kinetic optimization important to tissue-specific and whole-body function. This coupling is of paramount importance in the role that muscle plays in the success of Animalia. The structure and function of glycolytic enzyme complexes in anaerobic metabolism have long been regarded as a major regulatory element necessary for muscle activity and whole-body homeostasis. While the details of this complex remain to be elucidated through in vivo studies, this review will touch on recent studies that suggest the existence of such a complex and its structure. A potential model for glycolytic complexes and related subcomplexes is introduced.
Fatigue is a common symptom of numerous acute and chronic diseases, including myalgic encephalomy... more Fatigue is a common symptom of numerous acute and chronic diseases, including myalgic encephalomyelitis/chronic fatigue syndrome, multiple sclerosis, heart failure, cancer, and many others. In these multi-system diseases the physiological determinants of enhanced fatigue encompass a combination of metabolic, neurological, and myofibrillar adaptations. Previous research studies have focused on adaptations specific to skeletal muscle and their role in fatigue. However, most have neglected the contribution of physical inactivity in assessing disease syndromes, which, through deconditioning, likely contributes to symptomatic fatigue. In this commentary, we briefly review disease-related muscle phenotypes in the context of whether they relate to the primary disease or whether they develop secondary to reduced physical activity. Knowledge of the etiology of the skeletal muscle adaptations in these conditions and their contribution to fatigue symptoms is important for understanding the utility of exercise rehabilitation as an intervention to alleviate the physiological precipitants of fatigue.
Advances in experimental medicine and biology, 2005
Table 1 summarizes the primary mechanisms most likely responsible for modifying wing beat frequen... more Table 1 summarizes the primary mechanisms most likely responsible for modifying wing beat frequency (WBF) and muscle power in the Drosophila mutants discussed above. The different outcomes reflect different mechanisms that come into play, depending on the protein and site of the mutation. For example, the reduced muscle power and WBF of the RLC phosphorylation site mutant Mlc2(S6sA,S67A) reflect the reduced number of myosin heads available to form working cross-bridges and the concomitant reduction in muscle stiffness. The mixed results of the other mutants are more difficult to explain. For example, while the reduced muscle stiffness of the paramyosin rod mutant pm(S18A) and the projectin mutant bent(D)/+ may in part reflect mutation-related increases in compliance of the thick filaments (pm(S18A)) or connecting filaments (bent(D)/+), the elevated WBF is unexpected because one would expect reduced muscle stiffness to lower WBF rather than raise it. Other aspects of the results are ...
Advances in experimental medicine and biology, 2003
... Douglas M. Swank and David W. Maughan ... Because these rates are expressed as a stUn (2Jtb +... more ... Douglas M. Swank and David W. Maughan ... Because these rates are expressed as a stUn (2Jtb + 2m;) and product (21th x 21tc) in the transient solutions of the cross-bridge schemes presented below, we plotted both stUn and product as functions of [Pi], following the method of ...
Journal of muscle research and cell motility, 2001
The similarity of amino acid sequence and motifs of the N-terminal extensions of certain class II... more The similarity of amino acid sequence and motifs of the N-terminal extensions of certain class II myosin light chains, found throughout the animal kingdom, suggest a common functional role. One possible role of the N-terminal extension is to enhance oscillatory work and power production in striated muscles that normally operate in an oscillatory mode. We conducted small-angle X-ray diffraction experiments and small-length-perturbation analysis to examine the structural and functional consequences of deleting the N-terminal extension of the myosin regulatory light chain (RLC) in Drosophila flight muscle. The in vivo lattice spacing of dorsal longitudinal muscle (DLM) of flies lacking the RLC N-terminal extension (Dmlc2delta2-46) was approximately 1 nm less than that of wild type (48.56 +/- 0.02 nm). The myofilament lattice of detergent-treated, demembranated DLM swelled, with the DmlcdeltaA2-46 lattice expanding more than wild type and requiring roughly twice the concentration of Dex...
American journal of physiology. Heart and circulatory physiology, 2001
The role of altered cross-bridge kinetics during the transition from cardiac hypertrophy to failu... more The role of altered cross-bridge kinetics during the transition from cardiac hypertrophy to failure is poorly defined. We examined this in Dahl salt-sensitive (DS) rats, which develop hypertrophy and failure when fed a high-salt diet (HS). DS rats fed a low-salt diet were controls. Serial echocardiography disclosed compensated hypertrophy at 6 wk of HS, followed by progressive dilatation and impaired function. Mechanical properties of skinned left ventricular papillary muscle strips were analyzed at 6 wk of HS and then during failure (12 wk HS) by applying small amplitude (0.125%) length perturbations over a range of calcium concentrations. No differences in isometric tension-calcium relations or cross-bridge cycling kinetics or mechanical function were found at 6 wk. In contrast, 12 wk HS strips exhibited increased calcium sensitivity of isometric tension, decreased frequency of minimal dynamic stiffness, and a decreased range of frequencies over which cross bridges produce work an...
News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society, 1999
Substituting an alanine for serine in the regulatory subunit of the motor protein myosin dramatic... more Substituting an alanine for serine in the regulatory subunit of the motor protein myosin dramatically alters Drosophila's flight ability. Power output, at all levels of the flight system, is reduced. This example of deciphering a protein's function by producing malfunctions illustrates the broadening use of molecular genetics in integrative biology.
Uploads
Papers by David Maughan