Cooperative activation of skeletal and cardiac muscle.
Explore the source record for details and available documents.
Actin Cytoskeleton↗
Biomedical subjects
A M Gordon
Publications and source records attributed to A M Gordon.
Molecular and cellular aspects of muscle contraction. General discussion part II.
Explore the source record for details and available documents.
Animals↗
Motility assays of calcium regulation of actin filaments.
Explore the source record for details and available documents.
Actin Cytoskeleton↗
A simple model with myofilament compliance predicts activation-dependent crossbridge kinetics in skinned skeletal fibers.
The contribution of thick and thin filaments to skeletal muscle fiber compliance has been shown to be significant. If similar to the compliance of cycling cross-bridges, myofilament compliance could explain the difference in time course of stiffness and force during the rise of tension in a tetanus as well as the difference in Ca(2+) sensitivity of force and stiffness and more rapid phase 2 tension recovery (r) at low Ca(2+) activation. To characterize the contribution of myofilament compliance to sarcomere compliance and isometric force kinetics, the Ca(2+)-activation dependence of sarcomere compliance in single glycerinated rabbit psoas fibers, in the presence of ATP (5.0 mM), was measured using rapid length steps. At steady sarcomere length, the dependence of sarcomere compliance on the level of Ca(2+)-activated force was similar in form to that observed for fibers in rigor where force was varied by changing length. Additionally, the ratio of stiffness/force was elevated at lower force (low [Ca(2+)]) and r was faster, compared with maximum activation. A simple series mechanical model of myofilament and cross-bridge compliance in which only strong cross-bridge binding was activation dependent was used to describe the data. The model fit the data and predicted that the observed activation dependence of r can be explained if myofilament compliance contributes 60-70% of the total fiber compliance, with no requirement that actomyosin kinetics be [Ca(2+)] dependent or that cooperative interactions contribute to strong cross-bridge binding.
Actin Cytoskeleton↗
Objective assessment of progression in Huntington's disease: a 3-year follow-up study.
Objective measures to assess progression of Huntington's disease (HD) are desirable. The authors have previously found that patients with HD with higher Unified Huntington's Disease Rating Scale (UHDRS) motor scores exhibited higher variability of isometric grip forces while grasping an object. Therefore, the authors assessed grip force variability during this task in 10 HD patients with a 3-year follow-up. Grip force variability increased in all patients at the follow-up. Thus, grip force variability during grasping might be an objective and quantitative measure to assess motor deficits associated with the progression of HD.
Analysis of Variance↗
Altered movement trajectories and force control during object transport in Huntington's disease.
Individuals with Huntington's Disease (HD) have difficulty grasping and transporting objects, however, the extent to which specific impairments affect their performance is unknown. The present study examined the kinematics and force coordination during transport of an object in 12 subjects with HD and 12 age-matched controls. Subjects grasped an object between their thumb and index finger, transported it 25 cm forward, replaced and released it while their fingertip forces and the object's position were recorded. Five trials were performed with each of three weights (200 g, 400 g, and 800 g). While bradykinesia was evident in subjects with HD, this slowness was not consistently observed in all phases of the movement. The slowness of movement seen during the task appears to be due to impairments in sequencing and the movement strategies selected by the subjects. Compared to control subjects, subjects with HD produced highly curvilinear hand paths and more variable grip forces that were dependent on the weight of the object. Isometric force development and movement speed during transport were unaffected by the disease. The results suggest that prolonged task durations in subjects with HD are not necessarily due to slowness of movement, per se. These findings have clinical implications for understanding the task-specific nature of movement impairments in HD and developing effective intervention strategies.
Adult↗
Effector-dependent acquisition of novel typing sequences.
In an earlier report we found that when pairs of letters were physically transposed on the keyboard and typists were required to type letters in their new location, the disruptions in typing were reduced when the transpositions involved mirror movements of homologous fingers of the two hands compared with transpositions involving the same hand. We hypothesized that acquisition may be facilitated when a new movement mirrors a previously learned movement. In order to test this hypothesis, in the present study we transposed various pairs of letters between the two hands. Experienced typists (n = 6) typed phrases in which a key was physically transposed with another key on the keyboard and subjects typed the letters in their new location (for 200 trials). The pairs of transpositions involved: (1) similar movements of homologous fingers; (2) different movements of homologous fingers; (3) similar movements of non-homologous fingers; and (4) different movements of non-homologous fingers. After the transposition of keys, there were non-uniform prolongations in the typing intervals of words containing transposed keys, with the largest delay occurring directly before the transposition. Practice had a differential effect on these intervals; some key press intervals achieved control levels, while others did not improve at all. The disruptions in typing were dependent on the specific keys transposed. Transpositions involving non-homologous digits of the two hands were less disruptive than transpositions involving homologous digits. The results do not support our earlier hypothesis that acquisition may be facilitated when a new movement mirrors a previously learned one. These results provide some possible insights into how distinct levels of movement organization develop in typing as a result of practice. Furthermore, the non-uniformity of the typing intervals in the words containing transposed keys supports the notion that typing is organized at multiple levels, including the individual key press and word level.
Adult↗
Contribution of tactile information to accuracy in pointing movements.
We examined the contribution of tactile cues to accuracy during point-to-point movements. We used a task in which the experimenter guided either the left or right hand of the subject to a spatial location during the reference movement. During the subsequent test movement subjects were asked to point with the right hand to the remembered location without vision. Subjects contacted the target with their fingertip either during the reference movement, both the reference and test movements, or neither movement (i.e., the fingertip was held above the target surface). To differentiate between the contribution of tactile and proximal deep pressure information, the left index finger was anesthetized in a subsequent experiment. When subjects contacted the surface with the fingertip of the reference hand alone, error in movement direction decreased. When subjects made fingertip contact during the reference and test movements, gain error also decreased. Anesthesia of the fingertip degraded accuracy, suggesting that tactile information, independent of information from proximal deep pressure receptors, influenced movement accuracy. Thus, tactile information contributed to accuracy in pointing movements. We suggest that forces at fingertip contact may provide information regarding the orientation of the finger and forearm in space, which is used to replicate final arm posture. In addition, tactile cues at the beginning and end of the movement may be used to scale movement amplitude.
Adult↗
Initiation and development of fingertip forces during whole-hand grasping.
The present study examined the initiation of digit contact and fingertip force development during whole-hand grasping. Sixteen healthy subjects grasped an object instrumented with force transducers at each digit and lifted it 10 cm. The grip (normal) and load (tangential) forces and the position of the object were recorded. Twenty-five lifts were performed with various object weights (300 g, 600 g, 900 g) and surface textures (sandpaper and rayon). Despite the large number of degrees of freedom, grip initiation with an object using the whole hand was characterized by stereotypical contact patterns, which are idiosyncratic to each subject across all object weights and textures. However, in spite of the initial asymmetric control, the forces were mainly synchronized by the occurrence of the peak grip and load force rates. The contribution of each digit to the total grip force decreased from radial to ulnar digits. The final force distribution was generally established already at the onset of load forces. Only subtle adjustments were seen thereafter, suggesting a fairly fixed force distribution pattern throughout the grasp. The findings suggest that, despite the large number of degrees of freedom in terms of contact initiation and force distribution in whole-hand grasping: (1) subjects employ preferred movement patterns to establish object contact with their digits, and (2) synchronize the subsequent force development and temporal coordination of the task. Thus while the complexity of the task requires control mechanisms beyond those seen in two-finger precision grasping, there are strategies to simplify the complex task of the initiation and development of fingertip forces in whole-hand grasping.
Adult↗
Ca2+ - and cross-bridge-dependent changes in N- and C-terminal structure of troponin C in rat cardiac muscle.
Linear dichroism of 5'-tetramethylrhodamine (5'ATR)-labeled cardiac troponin C (cTnC) was measured to monitor cTnC structure during Ca2+-activation of force in rat skinned myocardium. Mono-cysteine mutants allowed labeling at Cys-84 (cTnC(C84), near the D/E helix linker); Cys-35 (cTnC(C35), at nonfunctional site I); or near the C-terminus with a cysteine inserted at site 98 (cTnC-C35S,C84S,S98C, cTnC(C98)). With 5'ATR-labeled cTnC(C84) and cTnC(C98) dichroism increased with increasing [Ca2+], while rigor cross-bridges caused dichroism to increase more with 5'ATR-labeled cTnC(C84) than cTnC(C98). The pCa50 values and n(H) from Hill analysis of the Ca2+-dependence of force and dichroism were 6.4 (+/-0.02) and 1.08 (+/-0.04) for force and 6.3 (+/-0.04) and 1.02 (+/-0.09) (n = 5) for dichroism in cTnC(C84) reconstituted trabeculae. Corresponding data from cTnC(C98) reconstituted trabeculae were 5.53 (+/-0.03) and 3.1 (+/-0.17) for force, and 5.39 (+/-0.03) and 1.87 (+/-0.17) (n = 5) for dichroism. The contribution of active cycling cross-bridges to changes in cTnC structure was determined by inhibition of force to 6% of pCa 4.0 controls with 1.0 mM sodium vanadate (Vi). With 5'ATR-labeled cTnC(C84) Vi caused both the pCa50)of dichroism and the maximum value at pCa 4.0 to decrease, while with 5'ATR-labeled cTnC(C98) the pCa50 of dichroism decreased with no change of dichroism at pCa 4.0. The dichroism of 5'ATR-labeled cTnC(C35) was insensitive to either Ca2+ or strong cross-bridges. These data suggest that both Ca2+ and cycling cross-bridges perturb the N-terminal structure of cTnC at Cys-84, while C-terminal structure is altered by site II Ca2+-binding, but not cross-bridges.
Animals↗
Influence of length on force and activation-dependent changes in troponin c structure in skinned cardiac and fast skeletal muscle.
Linear dichroism of 5' tetramethyl-rhodamine (5'ATR) was measured to monitor the effect of sarcomere length (SL) on troponin C (TnC) structure during Ca2+ activation in single glycerinated rabbit psoas fibers and skinned right ventricular trabeculae from rats. Endogenous TnC was extracted, and the preparations were reconstituted with TnC fluorescently labeled with 5'ATR. In skinned psoas fibers reconstituted with sTnC labeled at Cys 98 with 5'ATR, dichroism was maximal during relaxation (pCa 9.2) and was minimal at pCa 4.0. In skinned cardiac trabeculae reconstituted with a mono-cysteine mutant cTnC (cTnC(C84)), dichroism of the 5'ATR probe attached to Cys 84 increased during Ca2+ activation of force. Force and dichroism-[Ca2+] relations were fit with the Hill equation to determine the pCa50 and slope (n). Increasing SL increased the Ca2+ sensitivity of force in both skinned psoas fibers and trabeculae. However, in skinned psoas fibers, neither SL changes or force inhibition had an effect on the Ca2+ sensitivity of dichroism. In contrast, increasing SL increased the Ca2+ sensitivity of both force and dichroism in skinned trabeculae. Furthermore, inhibition of force caused decreased Ca2+ sensitivity of dichroism, decreased dichroism at saturating [Ca2+], and loss of the influence of SL in cardiac muscle. The data indicate that in skeletal fibers SL-dependent shifts in the Ca2+ sensitivity of force are not caused by corresponding changes in Ca2+ binding to TnC and that strong cross-bridge binding has little effect on TnC structure at any SL or level of activation. On the other hand, in cardiac muscle, both force and activation-dependent changes in cTnC structure were influenced by SL. Additionally, the effect of SL on cardiac muscle activation was itself dependent on active, cycling cross-bridges.
Animals↗
Skeletal and cardiac muscle contractile activation: tropomyosin "rocks and rolls".
Changes in thin filament structure induced by Ca(2+) binding to troponin and subsequent strong cross-bridge binding regulate additional strong cross-bridge attachment, force development, and dependence of force on sarcomere length in skeletal and cardiac muscle. Variations in activation properties account for functional differences between these muscle types.
Actin Cytoskeleton↗
Adaptive and dynamic control of respiratory and motor systems during object manipulation.
This investigation was designed to examine the relationship between breathing and prehension movements during object manipulation. Seated subjects (n=12) wore a facemask that was attached to a pneumotachometer which measured airflow. Initially, subjects completed baseline trials that were preceded and followed by an object lift. Subsequently, in response to an auditory signal the subjects reached forward, grasped and lifted an instrumented object that weighed either 150 g or 1000 g while their fingertip forces and movements were measured. The auditory signal was triggered by airflow in response to four experimental conditions (1) expiratory onset (2) inspiratory onset (3) mid-inspiration and (4) mid-expiration. Five trials for each of the four conditions were completed with each weight. The results revealed that inspiratory time was longer under baseline conditions after the subjects lifted the 150 g object as compared to the 1000 g object. In addition, the response latency and reach duration were significantly slower for the 150 g object compared to the 1000 g object during the experimental trials. These temporal measures were significantly correlated to inspiratory time for three of the four experimental conditions but no significant relationship with expiratory time was found. Lastly, lifting of the object occurred during expiration during most experimental conditions. We conclude that an adaptive process is formulated for both the motor and respiratory system in response to changes in motor output and/or sensory inputs associated with object manipulation, that might manifest itself in the pattern of breathing subsequent to removal of these stimuli. Furthermore, we suggest that motor inputs associated with the initiation of object manipulation interact with the control of respiratory timing so that the motor and respiratory systems are coupled. We speculate that this relationship may ensure that some motor tasks are performed during expiration to take advantage of changes in intrathoracic pressure that assist in postural maintenance during completion of the task.
Adaptation, Physiological↗
Action tremor during object manipulation in Parkinson's disease.
In previous studies of fingertip forces during precision grip in subjects with Parkinson's disease (PD), we observed regular oscillations in isometric force. The present study characterizes the nature of these oscillations. Fingertip forces were recorded from the index finger and thumb during precision grip-lifts with a 300 g and 900 g object in 10 subjects with PD and 20 healthy control subjects. Fourier analysis confirmed that all subjects with PD exhibited force oscillations with a clearly definable frequency (approximately 7-11 Hz). Five of these subjects also exhibited a second lower frequency peak (approximately 5 Hz). Approximately half of the 20 control subjects displayed a single frequency peak (approximately 8-12 Hz), which was generally lower in amplitude than in the subjects with PD (representing enhanced physiological tremor), whereas the remaining control subjects had low-amplitude, broad-based spectra (representing physiological tremor). The amplitude of the force oscillations was higher for lifts with the heavier object in both the control subjects and subjects with PD. L-Dopa resulted in a decreased tremor amplitude but did not influence the frequency. The force oscillations of the two opposing digits normal to the grip surfaces were in phase, whereas the oscillations tangential to the grip surfaces were often out of phase. The results suggest that the multipeaked force rate trajectories reported previously are caused by action tremor. The similarity of force oscillations in subjects with PD and healthy control subjects suggests common tremor-generating mechanisms and supports the notion that the parkinsonian action tremor (AT) is an exaggerated form of physiological tremor. These findings provide insight into the impaired hand function observed in individuals with PD.
Adult↗
Coordination of prehensile forces during precision grip in Huntington's disease.
The present study examined the coordination of prehensile forces during precision grip in subjects with Huntington's disease (HD). Fingertip forces were measured in 12 subjects with HD and 12 age-matched controls during the lifting of an instrumented object whose weight and surface texture were varied. The results indicate that subjects with HD have impaired initiation and delayed transitions between movement sequences and produce excessive and variable forces. However, subjects with HD demonstrated anticipatory scaling of force development based on the object's expected physical properties (planning) and adjustment of the force to the object's actual physical properties (sensorimotor integration). The observed findings generally were unrelated to the overall disease severity. However, the variability in forces was correlated with functional capacity and motor performance suggesting that variability is a key feature of the motor deficit. These results provide insights into the impaired hand function observed in individuals with HD.
Adult↗
Impaired force coordination during object release in children with hemiplegic cerebral palsy.
Recent studies on hand motor control in children with cerebral palsy (CP) have focused on the coordination of fingertip forces during the grasping and lifting of objects. However, little is known about the ability to replace and release an object from grasp, a function that is just as important for fine dexterity. The present study examines the coordination of fingertip forces during the replacement and release of an object (either 200 g or 400 g) from grasp in 14 children (aged between 7 and 13 years) with hemiplegic CP and in 14 age-matched typically developing children. The results indicate that children with hemiplegic CP abruptly replaced the object but had a prolonged and uncoordinated release of the grasp. Unlike what was seen in the control children, the grip and load forces decreased sequentially in the children with CP. However, all the children could appropriately scale the rate of force decrease based on somatosensory weight-related information from the ongoing lift. The results provide further information about the impaired hand skills in children with hemiplegic CP.
Adolescent↗
Specificity of internal representations underlying grasping.
The present study examines anticipatory control of fingertip forces during grasping based on the center of mass (CM) of a manipulated object. Subjects lifted an object using a precision grip while the fingertip forces and the angle about the vertical axis (roll) were measured. The object's CM could be shifted to the left or right of the object's center parallel to the grip axis without changing it's visual appearance. Subjects performed 20 lifts with the CM in the center, left, and right side of the object, respectively. Subjects were instructed to lift the object while preventing it from tilting. Within three to five lifts, subjects were able to asymmetrically partition the load force development before lift-off such that it was higher in the digit opposing the CM. This anticipatory load force partitioning prevented the object from rolling sideways at lift-off. To determine whether the internal representation underlying the anticipatory control is specific to the effectors used to form it, subjects performed five lifts with the right hand with the CM on one side. Following these lifts, they rotated the object 180 degrees around the vertical axis and performed one lift with the same hand or they translated the object to the left side of the body (with or without rotating it) and performed one lift with the left hand. Despite subjects' explicit knowledge of the new weight distribution, they were unable to appropriately scale the load forces at each digit, resulting in a subsequent large roll of the object. The findings suggest that within a few lifts subjects achieve a stable internal representation which accounts for the object's CM and is used to scale the fingertip forces in advance. They also suggest that this representation, which is used for anticipatory control of fingertip forces, is specific to the effectors used to form it. We propose that multiple internal representations may be used during the anticipatory control of grasping.
Adult↗
Regulation of contraction in striated muscle.
Ca(2+) regulation of contraction in vertebrate striated muscle is exerted primarily through effects on the thin filament, which regulate strong cross-bridge binding to actin. Structural and biochemical studies suggest that the position of tropomyosin (Tm) and troponin (Tn) on the thin filament determines the interaction of myosin with the binding sites on actin. These binding sites can be characterized as blocked (unable to bind to cross bridges), closed (able to weakly bind cross bridges), or open (able to bind cross bridges so that they subsequently isomerize to become strongly bound and release ATP hydrolysis products). Flexibility of the Tm may allow variability in actin (A) affinity for myosin along the thin filament other than through a single 7 actin:1 tropomyosin:1 troponin (A(7)TmTn) regulatory unit. Tm position on the actin filament is regulated by the occupancy of NH-terminal Ca(2+) binding sites on TnC, conformational changes resulting from Ca(2+) binding, and changes in the interactions among Tn, Tm, and actin and as well as by strong S1 binding to actin. Ca(2+) binding to TnC enhances TnC-TnI interaction, weakens TnI attachment to its binding sites on 1-2 actins of the regulatory unit, increases Tm movement over the actin surface, and exposes myosin-binding sites on actin previously blocked by Tm. Adjacent Tm are coupled in their overlap regions where Tm movement is also controlled by interactions with TnT. TnT also interacts with TnC-TnI in a Ca(2+)-dependent manner. All these interactions may vary with the different protein isoforms. The movement of Tm over the actin surface increases the "open" probability of myosin binding sites on actins so that some are in the open configuration available for myosin binding and cross-bridge isomerization to strong binding, force-producing states. In skeletal muscle, strong binding of cycling cross bridges promotes additional Tm movement. This movement effectively stabilizes Tm in the open position and allows cooperative activation of additional actins in that and possibly neighboring A(7)TmTn regulatory units. The structural and biochemical findings support the physiological observations of steady-state and transient mechanical behavior. Physiological studies suggest the following. 1) Ca(2+) binding to Tn/Tm exposes sites on actin to which myosin can bind. 2) Ca(2+) regulates the strong binding of M.ADP.P(i) to actin, which precedes the production of force (and/or shortening) and release of hydrolysis products. 3) The initial rate of force development depends mostly on the extent of Ca(2+) activation of the thin filament and myosin kinetic properties but depends little on the initial force level. 4) A small number of strongly attached cross bridges within an A(7)TmTn regulatory unit can activate the actins in one unit and perhaps those in neighboring units. This results in additional myosin binding and isomerization to strongly bound states and force production. 5) The rates of the product release steps per se (as indicated by the unloaded shortening velocity) early in shortening are largely independent of the extent of thin filament activation ([Ca(2+)]) beyond a given baseline level. However, with a greater extent of shortening, the rates depend on the activation level. 6) The cooperativity between neighboring regulatory units contributes to the activation by strong cross bridges of steady-state force but does not affect the rate of force development. 7) Strongly attached, cycling cross bridges can delay relaxation in skeletal muscle in a cooperative manner. 8) Strongly attached and cycling cross bridges can enhance Ca(2+) binding to cardiac TnC, but influence skeletal TnC to a lesser extent. 9) Different Tn subunit isoforms can modulate the cross-bridge detachment rate as shown by studies with mutant regulatory proteins in myotubes and in in vitro motility assays. (ABSTRACT TRUNCATED)
Animals↗