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Biomedical subjects

A M Gordon

Publications and source records attributed to A M Gordon.

At least 73 records · Page 4Linked to original sources
PubMed1993

Effects of inorganic phosphate analogues on stiffness and unloaded shortening of skinned muscle fibres from rabbit.

1. We examined the effects of aluminofluoride (AlFx) and orthovanadate (Vi), tightly binding analogues of orthophosphate (Pi), on the mechanical properties of glycerinated fibres from rabbit psoas muscle. Maximum Ca(2+)-activated force, stiffness, and unloaded shortening velocity (Vus) were measured under conditions of steady-state inhibition (up to 1 mM of inhibitor) and during the recovery from inhibition. 2. Stiffness was measured using either step or sinusoidal (1 kHz) changes in fibre length. Sarcomere length was monitored continuously by helium-neon laser diffraction during maximum Ca2+ activation. Stiffness was determined from the changes in sarcomere length and the corresponding changes in force. Vus was measured using the slack test method. 3. AlF chi and Vi each reversibly inhibited force, stiffness and Vus. Actively cycling cross-bridges were required for reversal of these inhibitory effects. Recovery from inhibition by AlF chi was 3- to 4-fold slower than that following removal of V1. 4. At various degrees of inhibition, AlF chi and Vi both inhibited steady-state isometric force more than either Vus or stiffness. For both AlF chi and Vi, the relatively greater inhibition of force over stiffness persisted during recovery from steady-state inhibition. We interpret these results to indicate that the cross-bridges with AlF chi or Vi bound are analogous to those which occur early in the cross-bridge cycle.

Aluminum↗
PubMed1993

Insulin-induced membrane changes in K(+)-depleted rat skeletal muscle.

Insulin-induced membrane changes were investigated in K(+)-depleted rat muscle. Male Sprague-Dawley rats were placed on a K(+)-free but otherwise adequate diet for 5-8 wk; serum K+ concentration ([K+]) dropped to 1.2-3.2 mM. Omohyoid membrane potential was -81 mV in 5.5 mM [K+] (SO4(2-)). Exposure to either insulin or low (0.5 mM) [K+] singly changed potential only slightly. The combination resulted in depolarization of 90% of fibers (-43 mV) and hyperpolarization of 10% of fibers (-101 mV). Fibers from normokalemic rats did not depolarize. Tetrodotoxin (TTX) blocked depolarization, implying the presence of noninactivating TTX-sensitive Na+ channels. K+ currents were measured using the three-electrode voltage clamp; movement of other ions was prevented by ion substitution, channel blockers, and depolarization-induced channel inactivation. K+ conductance was similar in control fibers with or without insulin. In the absence of insulin, currents in K(+)-depleted fibers were offset by a large leakage current that was significantly diminished when insulin was present. The insulin-induced current decrease was observed in nitrendipine, suggesting that the apparent decreased outward current was not an inward current carried by Ca2+. Data are consistent with altered Na+ and K+ channels in K(+)-depleted muscle, i.e., insulin-related closing of K+ channels initiates depolarization, which is then sustained by opening of noninactivating Na+ channels.

Animals↗
PubMed1993

Memory representations underlying motor commands used during manipulation of common and novel objects.

1. While subjects lifted a variety of commonly handled objects of different shapes, weights, and densities, the isometric vertical lifting force opposing the object's weight was recorded from an analog weight scale, which was instrumented with high-stiffness strain gauge transducers. 2. The force output was scaled differently for the various objects from the first lift, before sensory information related to the object's weight was available. The force output was successfully specified from information in memory related to the weight of common objects, because only small changes in the force-rate profiles occurred across 10 consecutive lifts. This information was retrieved during a process related to visual identification of the target object. 3. The amount of practice necessary to appropriately scale the vertical lifting and grip (pinch) force was also studied when novel objects (equipped with force transducers at the grip surfaces) of different densities were encountered. The mass of a test object that subjects had not seen previously was adjusted to either 300 or 1,000 g by inserting an appropriate mass in the object's base without altering its appearance. This resulted in either a density that was in the range of most common objects (1.2 kg/l) or a density that was unusually high (4.0 kg/l). 4. Low vertical-lifting and grip-force rates were used initially with the high-density object, as if a lighter object had been expected. However, within the first few trials, the duration of the loading phase (period of isometric force increase before lift-off) was reduced by nearly 50% and the employed force-rate profiles were targeted for the weight of the object.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Development of human precision grip. II. Anticipatory control of isometric forces targeted for object's weight.

The development of anticipatory control during lifts with the precision grip was examined in 100 children aged 1 to 15 years and in 15 adults. The children were instructed to lift an instrumented test object by using the precision grip between the thumb and index finger. The employed grip force, load force (vertical lifting force), vertical position and their corresponding time derivatives (i.e., grip and load force rates and acceleration) were recorded. The weight of the object was varied between trials to access the influence of the object's weight in the previous trial on the isometric force output. Already by the second year, children began to use information pertaining to the object's weight in the previous lift, i.e., they began to use an anticipatory control strategy. This occurred concomitant to the development of mainly bell shaped force rate profiles (Forssberg et al. 1991). The succeeding development of a more mature anticipatory control was gradual and adult-like capacity was not reached until 8-11 years of age.

Adolescent↗
PubMed1992

Development of human precision grip. III. Integration of visual size cues during the programming of isometric forces.

Recent evidence has shown that visual and haptical size information can be used by adults to estimate the weight of the object, forming the basis of the force programming during precision grip (Gordon et al. 1991a, b,). The present study examined the development of the capacity to use visual size information. In the first experiment, 30 children (age 1-7 years) and 10 adults performed a series of lifts with two boxes presented in an unpredictable order. The boxes were equal in weight but unequal in size and were attached to an instrumented grip handle which measured the employed grip force, load force, position and their corresponding time derivatives. The isometric force development was not influenced by the box size before the age of 3. However, the children aged 3 years and older demonstrated greater visual influences on the force programming than adults. To determine more precisely when children began to use visual size information, a second experiment in which the size and weight covaried was performed on 15 children. Children still did not use the size information during the force programming until the later half of the third year. It is concluded that this ability, probably involving associative transformations between the size and weight of objects, emerges around one year after anticipatory control based on somatosensory information pertaining to the weight of the object.

Adolescent↗
PubMed1992

Ca(2+)-dependence of structural changes in troponin-C in demembranated fibers of rabbit psoas muscle.

The Ca(2+)-dependence of structural changes in troponin-C (TnC) has been detected by monitoring the fluorescence from TnC labeled at Methionine-25, in the NH2-terminal domain, with danzylaziridine (TnC-DANZ) and then exchanged for endogenous TnC in glycerinated single fibers. The fluorescence-pCa relation obtained from fibers stretched to a sarcomere length greater than 4.0 microns evidenced two transitions: a small one, attributable to the binding of Ca2+ to the high affinity, Ca(2+)-Mg(2+)-binding sites of TnC; and a large one, attributable to the binding of Ca2+ to the low affinity, Ca(2+)-specific binding sites of TnC. In the fluorescence-pCa relation determined with fibers set to a sarcomere length of 2.4 microns, hence obtained in the presence of cycling cross-bridges, the large transition had the same Ca(2+)-dependence as did the development of tension. These results indicate that the NH2-terminal globular domain of TnC is modified by the binding of Ca2+ to sites located in both globular domains and that the structural changes in TnC resulting from the binding of Ca2+ to the low-affinity sites, but not to the high-affinity sites, are directly associated with the triggering of contraction.

Adenosine Triphosphate↗
PubMed1992

Force and stiffness in glycerinated rabbit psoas fibers. Effects of calcium and elevated phosphate.

Force (F) and stiffness (K) were measured in glycerinated psoas fibers at various calcium levels with 0, 10, 20, and 30 mM orthophosphate (Pi) added to the bathing solutions. The concentrations of bathing solution constituents were as follows: 110 mM potassium, 40 mM sodium, 4 mM MgATP, 10 mM total EGTA, and variable amounts of MOPS (pH buffer). The pH was 7.0, the ionic strength was 200 mM, and the temperature was 10 degrees C. Calcium levels were established by adding various amounts of CaCl2. All solutions contained 4% Dextran T-500. Fiber K was measured by imposing sinusoidal length changes (0.03-0.1%) at 1 kHz and by applying rapid steps in length and measuring the resulting F changes. At all [Pi] tested, K was more sensitive to calcium than F. Elevating bathing solution [Pi] caused a decrease in the calcium sensitivity of both F and K, while the slopes of F-calcium and K-calcium relations increased. In maximally activating calcium, raising [Pi] caused a continuous decrease in F over the range tested, while from very low to 10 mM Pi K remained constant. Above 10 mM Pi K declined, but to a lesser extent than did F. The results suggest that under our experimental conditions strongly attached crossbridges can exist in both force-producing and non-force-producing states, and that the relative population of these states may be calcium dependent.

Actins↗
PubMed1992

Impaired anticipatory control of isometric forces during grasping by children with cerebral palsy.

The authors examined the force regulation during prehension of 12 children with cerebral palsy (CP) and an age-matched control group. The control group appropriately scaled the isometric force output in one force-rate pulse toward the weight of the previously lifted object, but children with CP exhibited stepwise increases in force in which the force amplitudes were not influenced by the object's weight. When the object was held in the air, most children with CP were able to modify their force output according to the object's weight, using sensory feedback, but their forces were more variable than those of the control group and less influenced by the object's weight. Although children with CP have disturbed sensory feedback--likely to lead to an indistinct internal representation of an object's physical properties--their main disability stems from impaired central co-ordination of motor activity.

Biomechanical Phenomena↗
PubMed1992

Effects of cycling and rigor crossbridges on the conformation of cardiac troponin C.

The results of work by several investigators indicate that crossbridge attachment serves as a positive feedback mechanism that transiently increases the Ca2+ affinity of troponin C (TnC) during each normal heartbeat. To monitor structural changes in the cardiac isoform of TnC (cTnC) associated with Ca2+ binding and crossbridge attachment in muscle, we labeled cTnC with the sulfhydryl-specific fluorescent probe 2-(4'-iodoacetamidoanilino)naphthalene-6-sulfonic acid (IAANS). When IAANS-labeled cTnC (cTnCIAANS) was substituted for endogenous TnC, the fluorescence intensity of cardiac and skeletal muscle preparations increased substantially during rigor crossbridge attachment in the absence of Ca2+ (pCa 9.2). In cardiac muscle, the fluorescence signal increased the same amount in rigor and maximal activation, whereas in skeletal muscle, it was higher in rigor (rigor: cardiac and skeletal = 1; pCa 4.0: cardiac = 0.98 +/- 0.13, skeletal = 0.59 +/- 0.05). This indicates that crossbridge attachment alone is capable of influencing the structure of cTnCIAANS. Because the relative fluorescence intensity of cTnCIAANS was more sensitive to Ca2+ than was force in both preparations (cardiac: pCa50 fluorescence = 6.05 +/- 0.05, pCa50 force = 5.51 +/- 0.11; skeletal: pCa50 fluorescence = 5.94 +/- 0.13, pCa50 force = 5.65 +/- 0.14), we measured the Ca2+ sensitivity of the strong crossbridge attachment (sinusoidal stiffness was measured by imposing 1 kHz at 0.1-0.2% muscle length) in rat trabeculae.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Deletion of the first 45 NH2-terminal residues of rabbit skeletal troponin T strengthens binding of troponin to immobilized tropomyosin.

The binding of the NH2-terminal region of troponin T (TnT) to the COOH-terminal region of tropomyosin (Tm) and the head-to-tail overlap between Tm molecules is thought to provide a pivotal link between troponin (Tn) and Tm (White, S.P., Cohen, C., and Phillips, G.N., Jr. (1987) Nature 325, 826-828). To further explore the structure-function relationship of the NH2-terminal region of TnT, we studied the binding of a 26,000-dalton TnT fragment (26K-TnT, Ohtsuki, I., Shiraishi, F., Suenaga, N., Miyata, T., and Tanokura, M.J. (1984) J. Biochem. (Tokyo) 95, 1337-1342) which corresponds to residues 46-259 of TnT2f, the major isoform of TnT in rabbit fast twitch muscle, to immobilized alpha-Tm. Both 26K-TnT and TnT2f were retained by the alpha-Tm affinity column in the presence of 150 mM NaCl. However, upon increasing the NaCl concentration 26K-TnT was eluted from the column at a higher ionic strength than was TnT. When applied alone, the binary complex of TnI and TnC (TnC.TnI) was not retained by the alpha-Tm affinity column. When applied subsequently to prebound TnT2f or 26K-TnT, TnI.TnC was retained by the alpha-Tm affinity column and eluted together with TnT2f or 26K-TnT as ternary troponin complexes. Whether Ca2+ was present or not, Tn containing 26K-TnT was eluted at a higher ionic strength than was Tn containing TnT2f, indicating that removal of the first 45 residues of TnT2f strengthens the binding of Tn to Tm. In the presence of Tm, reconstituted Tn containing 26K-TnT conferred Ca2+ sensitivity on actomyosin-S1 MgATPase, and the steepness of the pCa-ATPase relation was unchanged with respect to the actoS1 ATPase regulated by TnT2f. It is concluded that the first 45 residues of TnT2f are not essential for anchoring the troponin complex to the thin filament and do not play a crucial role in the cooperative response of regulated actoS1 ATPase to Ca2+.

Amino Acids↗
PubMed1991

Visual size cues in the programming of manipulative forces during precision grip.

A size-weight illusion was used to examine the role of visual cues in the programming of manipulative forces during the lifting of test objects utilizing the precision grip. Three different boxes of equal weight and unequal size were lifted. These were equipped with an instrumented grip handle to measure the employed grip force, load force (vertical lifting force), force rates and vertical movement. All fifteen subjects participating in the study reported that the smallest box was the heaviest, which is consistent with size-weight illusion predictions. However, the rate of increase of the isometric grip and load forces initially during the lift, the peaks of the grip and load force and the vertical acceleration were all found to increase with the box size. Thus, despite the conscious perception indicating a heavier weight for the small object, the motor program was scaled for a lighter weight. Yet, no differences were found in grip force during the static phase of the lift, where weight related information was apparently available via sensory feedback. Previous studies have reported that the programming of the precision grip is based on somatosensory information gained during previous lifts (Johansson and Westling 1984, 1988a, b). The present study suggests that visual cues are integrated in the programming of manipulative forces during precision grip.

Adult↗
PubMed1991

The integration of haptically acquired size information in the programming of precision grip.

Recent evidence for the use of visual cues in the programming of the precision grip has been given by Gordon et al. (1991). Visually invoked size-related information influenced the physical forces used to produce a lift, even when it was not consistent with other sensory information. In the present study, blind-folded subjects were required to feel the size of an object by haptic exploration prior to lifting it. Two boxes of equal weight and unequal size were used for the lift objects and were attached to an instrumented (grip) handle. Grip force and load force, their rates, and the vertical movement of the object were measured. Most subjects reported that the small box was heavier, which is consistent with size-weight illusion predictions. However, peak grip force, grip force rate, peak load force, and load force rate were greater for the large box when the boxes were randomly presented, but not when the same boxes were lifted consecutively. If subjects did not feel the box prior to a lift, these parameters were scaled in between those normally employed for the large and small box. Most subjects apparently programmed the parallel increase of the grip and load force during the loading phase as one force rate pulse. This represented a "target strategy" in which an internal neural representation of the objects weight determined the actual target parameter (i.e. just enough force required to overcome gravity). The other subjects exhibited a slower stepwise increase in grip and load force rate. The subjects choosing this "probing strategy" did not scale the force parameters differently for the two boxes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Integration of sensory information during the programming of precision grip: comments on the contributions of size cues.

Evidence has recently been given by Gordon et al. (1991a, b) for the use of visually and haptically acquired information in the programming of lifts with the precision grip. The size-related information influences the development of manipulative forces prior to the lift-off, and the force output for larger objects is adjusted for a heavier weight even if the weight of the objects is kept the same. However, the size influences on the force output were small compared to the relative effects of the expected weight in previous trials (Johansson and Westling 1988). In the present study, both the size and weight of objects were changed between consecutive lifts to more fully determine the strength of visual size cues. During most trials, the size and weight covaried (i.e. the weight was proportional to the volume). However, in some trials, only the size was switched while the weight was kept the same to create a mismatch between the size and weight. The forces were still appropriately scaled towards an expected weight proportional to the volume of the object. It was concluded that visual size cues are highly purposeful. The effects were much larger than previously reported and were similar in magnitude to the effects based upon the expected weight. Thus, the small effects reported in the previous experiments may have been a result of conflicting "size-weight" information.

Adolescent↗
PubMed1991

Basic co-ordination of manipulative forces of children with cerebral palsy.

The coordination of manipulatory forces during prehension was studied in 12 children with cerebral palsy (CP) and compared with that of controls. The results indicated that coupling of grip force and load force does not develop in children with CP. These children's force development increased in stages, with an early onset of excessive grip force. They did not use anticipatory control of the isometric force development during the load phase. Prolonged delays between successive phases indicated inefficient sensory feedback during the movement. The early onset of grip force and the over-all high force employment may compensate for the lack of anticipatory control and inefficient sensorimotor integration.

Cerebral Cortex↗
PubMed1990

Stretch of active muscle during the declining phase of the calcium transient produces biphasic changes in calcium binding to the activating sites.

In voltage-clamped barnacle single muscle fibers, muscle shortening during the declining phase of the calcium transient increases myoplasmic calcium. This extra calcium is probably released from the activating sites by a change in affinity when cross-bridges break (Gordon, A. M., and E. B. Ridgway, 1987. J. Gen. Physiol. 90:321-340). Stretching the muscle at similar times causes a more complex response, a rapid increase in intracellular calcium followed by a transient decrease. The amplitudes of both phases increase with the rate and amplitude of stretch. The rapid increase, however, appears only when the muscle is stretched more than approximately 0.4%. This is above the length change that produces the breakpoint in the force record during a ramp stretch. This positive phase in response to large stretches is similar to that seen on equivalent shortening at the same point in the contraction. For stretches at different times during the calcium transient, the peak amplitude of the positive phase has a time course that is delayed relative to the calcium transient, while the peak decrease during the negative phase has an earlier time course that is more similar to the calcium transient. The amplitudes of both phases increase with increasing strength of stimulation and consequent force. When the initial muscle the active force. A large decrease in length (which drops the active force to zero) decreases the extra calcium seen on a subsequent restretch. After such a shortening step, the extra calcium on stretch recovers (50 ms half time) toward the control level with the same time course as the redeveloped force. Conversely, stretching an active fiber decreases the extra calcium on a subsequent shortening step that is imposed shortly afterward. Enhanced calcium binding due to increased length alone cannot explain our data. We hypothesize that the calcium affinity of the activating sites increases with cross-bridge attachment and further with cross-bridge strain. This accounts for the biphasic response to stretch as follows: cross-bridges detached by stretch first decrease calcium affinity, then upon reattachment increase calcium affinity due to the strained configuration brought on by the stretch. The experiments suggest that cross-bridge attachment and strain can modify calcium binding to the activating sites in intact muscle.

Aequorin↗