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Biomedical subjects

M E Houston

Publications and source records attributed to M E Houston.

At least 37 records · Page 2Linked to original sources
PubMed1995

Myosin phosphorylation augments force-displacement and force-velocity relationships of mouse fast muscle.

Two studies were conducted to examine the effect of myosin regulatory light chain (R-LC) phosphorylation on the rate and extent of shortening in submaximally activated mouse extensor digitorum longus muscles in vitro at 25 degrees C. For each study, R-LC phosphate content was increased fivefold by application of a 5-Hz, 20-s conditioning stimulus (CS) to 0.65-0.68 mol phosphate/mol R-LC; this level was sustained between 10 and 40 s after the CS. Maximum isometric twitch force and the maximum rate of force development (+dF/dtmax) were potentiated in the range 13-17% and 9-17% (P < 0.05), respectively, after the CS. In study 1, the maximal rate and extent of shortening were significantly enhanced by 10 and 21% (P < 0.001), respectively, when measured using a twitch zero-load clamp technique. In study 2, the force-velocity and force-displacement relationships were both augmented when determined with the twitch afterload technique. Displacement was enhanced between 20 and 82% for loads that ranged from 3 to 75% of active peak twitch force, whereas velocity was increased 6-8% over the same range (P < 0.05), including the predicted maximum velocity (Vmax; 5.08 vs. 4.69 muscle length/s). In both studies the increase in velocity likely represents a shift along the force-velocity relationship toward true Vmax that reflects a decrease in relative load due to force potentiation. Furthermore, with the decrease in relative load, displacement at a given load was also increased. Potentiated displacement and extent of R-LC phosphorylation also decreased in parallel when studied for 5 min after the CS. The increase in muscle shortening is a novel finding and suggests a function for R-LC phosphorylation with respect to movement because both peak work and power were also enhanced by up to 22%. These effects are consistent with an R-LC phosphorylation-induced increase in fapp, the apparent rate constant that describes the cross-bridge transition from the non-force-generating to the force-generating state.

Animals↗
PubMed1995

Vitamin E status and response to exercise training.

Vitamin E is an important intramembrane antioxidant and membrane stabiliser. Over the past 40 years, vitamin E supplementation has been advocated for athletes in the hope of improving performance, minimising exercise-induced muscle damage and maximising recovery. However, there is currently a lack of conclusive evidence that exercise performance or recovery would benefit in any significant way from dietary vitamin E supplementation. Exceeding current recommended intakes of vitamin E even by several orders of magnitude will result in relatively modest increases in tissue or serum vitamin E concentrations. Most evidence suggests that there is no discernible effect of vitamin E supplementation on performance, training effect or rate of postexercise recovery in either recreational or elite athletes. There is very little evidence, particularly involving humans, that exercise or training will significantly alter tissue or serum vitamin E levels. While there is some evidence that certain indices of tissue peroxidation may be reduced following dietary vitamin E supplementation, the physiological and performance consequences in humans of these relatively minor effects are unknown. Although there appears to be little reason for vitamin E supplementation among athletes, it does not appear that the practice of supplementation is harmful.

Animals↗
PubMed1994

Contractile properties of rat gastrocnemius muscle during staircase, fatigue and recovery.

Slowing of relaxation is one of the anticipated changes in the contraction of fatigued skeletal muscle. However, interpretation of the mechanism(s) contributing to slowed relaxation may be affected by the measurement technique employed. In this study, relaxation was measured in three ways: (i) traditional half-relaxation time; (ii) peak rate of relaxation; and (iii) late relaxation time, measured from 50 to 25% of peak developed tension. When rat gastrocnemius muscle was stimulated indirectly in situ at 10 Hz, developed tension increased in 10 s to 185%, then decreased to 39% after 1 min with little additional change over the next 4 min. After 10 s of inactivity, developed tension was 60% of the initial value, but did not recover further over the next 20 min. The half-relaxation time transiently decreased at the start of stimulation, then by 20 s was considerably prolonged. Within 10 s of recovery, half-relaxation time returned to prestimulation values but became prolonged again by 10 min of recovery. The peak rate of relaxation was proportional to the developed tension at all times except 2.5-10 s of 10 Hz stimulation, at which time acceleration of relaxation was evident, and 15-20 s of the 10 Hz stimulation when it was relatively decreased. The late relaxation time increased during the repetitive stimulation, returned to control level early in recovery, then increased again, by 5 min of recovery. The diverse responses indicated by these indices of relaxation potentially discriminate different mechanisms which contribute to slowing of relaxation in fatigue, a point which would be missed if a single method of measurement of relaxation was employed.

Animals↗
PubMed1994

Role of sarcoplasmic reticulum in loss of load-sensitive relaxation in pressure overload cardiac hypertrophy.

The loss of load-sensitive relaxation observed in the pressure-overloaded heart may reflect a strategy of slowed cytosolic Ca2+ uptake to yield a prolongation of the active state of the muscle and a decrease in cellular energy expenditure. A decrease in the potential of the sarcoplasmic reticulum (SR) to resequester cytosolic Ca2+ during diastole could contribute to this attenuated load sensitivity. To test this hypothesis, both in vitro mechanical function of anterior papillary muscles and the SR Ca2+ sequestration potential of female guinea pig left ventricle were compared in cardiac hypertrophy (Hyp) and sham-operated (Sham) groups. Twenty-one days of pressure overload induced by coarctation of the suprarenal, subdiaphragmatic aorta resulted in a 36% increase in left ventricular mass in the Hyp. Peak isometric tension, the rate of isometric tension development, and the maximal rates of isometric and isotonic relaxation were significantly reduced in Hyp. Load-sensitive relaxation were significantly reduced in Hyp. Load-sensitive relaxation quantified by the ratio of a rapid loading to unloading force step in isotonically contracting papillary muscle was reduced 50% in Hyp muscles. Maximum activity of SR Ca(2+)-adenosinetriphosphatase (ATPase) measured under optimal conditions (37 degrees C; saturating Ca2+) was unaltered, but at low free Ca2+ concentrations (0.65 microM), it was decreased by 43% of the Sham response. Bivariate regression analysis revealed a significant (r = 0.84; P = 0.009) relationship between the decrease in SR Ca(2+)-ATPase activity and the loss of load-sensitive relaxation after aortic coarctation. Stimulation of the SR Ca(2+)-ATPase by the catalytic subunit of adenosine 3',5'-cyclic monophosphate-dependent protein kinase resulted in a 2.6-fold increase for Sham but only a 1.6-fold increase for Hyp. Semiquantitative Western blot radioimmunoassays revealed that the changes in SR Ca(2+)-ATPase activity were not due to decreases in the content of the Ca(2+)-ATPase protein or phospholamban. Our data directly implicate a role for decreased SR function in attenuated load sensitivity. A purposeful downregulation of SR Ca2+ uptake likely results from a qualitative rather than a quantitative change in the ATPase and possibly one of its key regulators, phospholamban.

Animals↗
PubMed1994

Antioxidant and oxidative enzyme adaptations to vitamin E deprivation and training.

The effects of endurance training on tissue antioxidant and oxidative enzyme activities were determined in heart, liver, and five skeletal muscles of female rats. Rats were fed either normal (+E) or vitamin E free (-E) diets for 16 wk. For the final 8 wk, subgroups of +E and -E diet animals were trained by treadmill running at 40 m.min-1, 15% grade for 60 min.d-1. No significant differences in training abilities were observed between diet groups. Endurance training significantly increased citrate synthase (CS) activity in all skeletal muscles for both the +E and -E diet animals with no significant difference in degree of response between diet groups. Neither vitamin E deprivation, training, or their combination generally affected the activities of the antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), or glutathione peroxidase (GPX) in skeletal muscles, heart, or liver of the animals. These results suggest that despite an anticipated increase in free radical induced tissue "oxidative stress" brought about by a combination of vitamin E deprivation and endurance training, antioxidant enzyme adaptations were not evident and the response of citrate synthase to training was not impaired in female rats.

Adaptation, Physiological↗
PubMed1993

Myosin light chain phosphorylation during staircase in fatigued skeletal muscle.

It has been reported that the peak of the staircase or the enhanced tension response during low frequency stimulation is delayed in fatigued fast muscle. Our purpose was to determine if the rate and extent of regulatory myosin light chain (P-LC) phosphorylation, a molecular mechanism associated with the positive staircase, are also altered by fatigue. The staircase contractile response, muscle metabolites and phosphate incorporation by the P-LC were assessed at 0, 5, 10 or 20 s of 10-Hz stimulation, in either non-fatigued (control) or fatigued (10 Hz for 5 min, followed by 20 min of recovery) rat gastrocnemius muscle in situ. The concentration of adenosine triphosphate (ATP) in fatigued muscles, 21 +/- 0.9 mmol.kg-1 (dry weight) was significantly lower (P < 0.05) than in the control muscles, 26.1 +/- 1.5 mmol.kg-1. In both groups, ATP content was significantly lower after 20 s of 10 Hz stimulation. The P-LC phosphate content (in mol phosphate.mol-1 P-LC) was 0.10, 0.38, 0.60 and 0.72 after 0, 5, 10 or 20 s of 10 Hz stimulation in control muscles, but only 0.03, 0.08, 0.11 and 0.19 at these times in fatigued muscles. Although the absolute magnitude of tension potentiation was attenuated in proportion to the depressed twitch amplitude, these surprisingly low levels of phosphorylation were associated with 0, 48, 79 and 86% potentiation of the developed tension at these times in contrast with 0, 71, 87 and 49% potentiation in control muscles. These data demonstrate that while the rate and extent of phosphate incorporation is depressed in fatigued muscle, tension potentiation is still evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

Vitamin E status does not affect the responses to exercise training and acute exercise in female rats.

Responses of vitamin E-depleted female rats to acute exercise and chronic exercise training were tested. Rats were fed either a control diet (+E rats) or a vitamin E-depleted diet (-E rats). After 8 wk, subgroups of the +E and -E rats performed treadmill exercise for 45 min at 28 m/min, 15% grade, and were immediately killed. Vitamin E concentrations were 80-90% lower in liver, heart and muscles in -E rats as determined by HPLC. There was no difference between +E and -E rats in blood lactate concentration, creatine kinase, lipid peroxidation indices, hematocrit or hemoglobin concentration following acute exercise. Remaining rats were either trained for a further 8 wk at 40 m/min, 15% incline for up to 60 min/d or served as untrained controls. No differences in training tolerance were seen between diet groups, with 64% of +E rats and 71% of -E rats consistently completing 60 min of daily training. The training induced similar adaptive elevations in succinate dehydrogenase activity (31-107%) in various hind limb muscles of both +E and -E rats. Trained +E rats had lower vitamin E concentrations in some but not all tissues when compared with untrained +E controls. These results suggest that consumption of a vitamin E-free diet for 8 wk did not result in differences in blood indices associated with exercise stress or in the ability to perform a submaximal acute exercise test when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Physiological significance of myosin phosphorylation in skeletal muscle.

Each S-1 or head portion of the myosin molecule in skeletal muscle contains a subunit known as the regulatory or phosphorylatable light chain (P-LC). Phosphorylation of the P-LC is mediated by the second messenger Ca2+ and takes place when the muscle fibre is activated. In smooth muscle, phosphorylation of the P-LC is the principal mechanism that initiates contraction, but in skeletal muscle myosin P-LC phosphorylation is not required for contraction and a definitive role has not been established. It has been proposed that P-LC phosphorylation modulates the intrinsic nature of actin-myosin interactions, leading to force potentiation under suboptimal activation conditions. An example of this is posttetanic potentiation. This paper describes a P-LC phosphorylation induced mechanism for force enhancement during isometric contraction. In addition, it summarizes recent data revealing that P-LC phosphorylation is associated with enhanced work output of fast-twitch muscle during shortening and lengthening contractions.

Actins↗
PubMed1993

Threshold for force potentiation associated with skeletal myosin phosphorylation.

Phosphate incorporation by the phosphorylatable light chains (P-LC) of myosin is associated with isometric twitch force potentiation in intact fast-twitch muscle. The purpose of this study was to examine the association between myosin P-LC phosphorylation and force potentiation at higher stimulation frequencies (1-150 Hz) using mouse extensor digitorum longus (EDL) muscles at 25 degrees C. Peak isometric force and the peak rate of isometric force development (+dF/dtmax) were measured at selected test frequencies before and after the application of a 5-Hz 20-s conditioning stimulation known to increase P-LC phosphate content. Associated with a ninefold elevation in myosin P-LC phosphate content (to 0.72 mol phosphate/mol P-LC), +dF/dtmax was increased at all test frequencies (mean 27%, range 20-37%). After the conditioning stimulus, peak isometric force was increased by approximately 15% for frequencies 1-15 Hz. However, at 20-150 Hz, the increase in +dF/dtmax was not associated with force potentiation, since peak force was diminished by 5-40%. These data reveal that the stimulation frequency limit for the potentiation of peak force production associated with myosin P-LC phosphorylation is < 20 Hz in mouse EDL at 25 degrees C. Furthermore, the data suggest that increases in the rate constant describing the rate of cross-bridge transition from a non-force-generating to a force-generating state mediated by myosin P-LC phosphorylation may be responsible for the general increase in +dF/dtmax and for the force potentiation at 1-15 Hz.

Animals↗
PubMed1992

Chronic low frequency stimulation reduces myosin phosphorylation in rabbit fast twitch muscle.

The effect of 1-12 days of electrical stimulation (10 Hz) on the ability to phosphorylate the P-light chain of myosin was studied in rabbit tibialis anterior muscle. Myosin phosphorylation was induced by exposure of the stimulated muscle and that of the contralateral leg to a single conditioning stimulus train (5 Hz) for 25 s via the motor nerve. Isometric tension was measured as were the myosin light chain composition and the activities of the enzymes responsible for phosphorylation and dephosphorylation. A computer simulation of the potential effect of a stimulation-induced disruption of Ca2+ metabolism on phosphorylation was also performed. Chronic stimulation for as little as 1 day eliminated light chain phosphorylation and reduced the myosin light chain kinase activity by approximately 36%. Conversely, phosphatase activity and light chain composition were unaffected. The model demonstrated that a slight depression in the magnitude of the Ca2+ transient could potentially attenuate phosphorylation. The data suggest that phosphorylation of myosin is extremely sensitive to prolonged muscle activity. Furthermore, it appears more likely that this sensitivity is related to regulation of intracellular free Ca2+ than to the other elements of the calmodulin-dependent system for myosin phosphorylation examined.

Animals↗
PubMed1992

Overtraining.

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Exercise↗
PubMed1991

Energy metabolism in human slow and fast twitch fibres during prolonged cycle exercise.

1. The effects of prolonged exercise on energy metabolism in type I and type II muscle fibres in the vastus lateralis muscle were investigated in six male subjects (20.0 +/- 0.5 years, mean +/- S.E.M.) who performed one-legged cycling at 61% of maximum O2 consumption (VO2,max; determined with one leg) until fatigue or for a maximum of 2 h. 2. Analysis of pools of freeze-dried fibres obtained by needle biopsy and separated into specific types by the myofibrillar ATPase histochemical procedure indicated higher (P less than 0.05) lactate concentrations in type II fibres compared to type I fibres at 15 min (43.9 +/- 9.7 and 51.2 +/- 9.8 mmol (kg dry wt)-1) and at 60 min (18.2 +/- 4.7 and 25.9 +/- 6.5 mmol (kg dry wt)-1). No differences existed in lactate concentration between fibre types for pre-exercise (10.0 +/- 1.6 and 13.3 +/- 2.8 mmol (kg dry wt)-1) or post-exercise. 3. Glycogen degradation was most pronounced in type I fibres. By the end of exercise, glycogen concentration was 82.4 +/- 45 mmol glucosyl units (kg dry wt)-1 in type I fibres and 175 +/- 62 mmol glucosyl units (kg dry wt)-1 in type II fibres. 4. No significant changes in ATP and creatine phosphate (CrP) were found in either fibre type with exercise. 5. It is concluded that, at least for lactate and glycogen, fibre-specific differences are evident in prolonged submaximal exercise. The cause of the difference probably relates both to the unique energy metabolic characteristics of each fibre type and to the manner in which they are utilized during the exercise. 6. The failure to find a reduction in ATP concentration in either fibre type during prolonged exercise in the face of a progressive increase in the number of fibres showing little or no glycogen concentration suggests that protective mechanisms exist that prevent an energy crisis. The nature of these protective mechanisms remains to be elucidated.

Adenosine Triphosphate↗
PubMed1991

Torque potentiation and myosin light-chain phosphorylation in human muscle following a fatiguing contraction.

Indices of electrically stimulated and maximal voluntary isometric muscle torgue and the phosphate content of myosin phosphorylatable light chains (P light chains) were studied during recovery following a 60-s maximal voluntary isometric contraction (MVC) in 21 human subjects. Analysis of muscle biopsy samples revealed that immediately after the 60-s MVC there were significant decreases in ATP (-15%) and phosphocreatine (-82%), and lactate concentration increased by 17-fold. All indices of muscle torque production were reduced by the 60-s MVC, but the twitch torque and torque at 10 Hz were relatively less reduced compared with the torque at 20 and 50 Hz or a 1-s MVC. Between 3 and 6 min of recovery, twitch torque and torque at 10 Hz stimulation were significantly potentiated, reaching peak values of 125 and 134%, respectively, compared with rest. Phosphate content of the fast and two slow P light chains was significantly increased over rest levels immediately after and 4 min after the 60-s MVC. These results suggest that myosin P light-chain phosphorylation could provide a mechanism to increase human muscle torque under conditions of submaximal contractile element activation following fatigue.

Adenosine Triphosphate↗
PubMed1991

Simultaneous potentiation and fatigue in quadriceps after a 60-second maximal voluntary isometric contraction.

Potential mechanisms of fatigue (metabolic factors) and potentiation (phosphate incorporation by myosin phosphorylatable light chains) were investigated during recovery from a 60-s maximal voluntary isometric contraction (MVC) in the quadriceps muscle of 12 subjects. On separate days before and for 2 h after the 60-s MVC, either a 1-s MVC or electrically stimulated contractions were used as indexes to test muscle performance. Torque at the end of the 60-s MVC was 57% of the initial level, whereas torques from a 1-s MVC and 50-Hz stimulation were most depressed in the immediate recovery period. At this time, muscle biopsy analyses revealed significant decreases in ATP and phosphocreatine and a 19-fold increase in muscle lactate. Conversely, isometric twitch torque and torque from a 10-Hz stimulus were the least depressed of six contractile indexes and demonstrated potentiation of 25 and 34%, respectively, by 4 min of recovery (P less than 0.05). At this time, muscle lactate concentration was still 16 times greater than at rest. An increased phosphate content of the myosin phosphorylatable light chains (P less than 0.05) was also evident both immediately and 4 min after the 60-s MVC. We conclude that the 60-s MVC produced marked force decreases likely due to metabolic displacement, while the limited decline in the twitch and 10-Hz torques and their significant potentiation suggested that myosin phosphorylation may provide a mechanism to enhance contractile force under conditions of submaximal activation during fatigue.

Adenosine Triphosphate↗
PubMed1990

Myosin phosphorylation, twitch potentiation, and fatigue in human skeletal muscle.

Twitch tension and phosphate incorporation into the phosphorylatable light chains (P-light chains) of myosin were studied during a 10-min recovery period following a 10- or 60-s maximal voluntary isometric contraction (MVC) in 18 subjects. Analysis of muscle biopsy samples obtained before, immediately after, 1 min, and 10 min following the 10-s MVC revealed that the 10-s MVC produced a modest but transient metabolic displacement from rest, a 35% decrease in phosphocreatine, and a threefold elevation in lactate concentration. Immediately after the 60-s MVC, ATP was decreased by 20%, phosphocreatine decreased by 84%, and lactate was elevated by 15-fold. Lactate remained elevated over the 10-min recovery period. Twitch force was maximally potentiated following the 10-s MVC and declined to rest by 10 min of recovery. Twitch force was 0.66 of rest value immediately after the 60-s MVC, then increased over the next 4 min to reach a potentiated value 21% greater than rest, before declining. Significant phosphate incorporation into P-light chains was observed immediately after both contractions, but dephosphorylation to rest values at the end of recovery was only noted for the 60-s condition. These results demonstrate an inconsistent relationship between twitch tension enhancement and P-light chain phosphorylation in the in vivo human model.

Adenosine Triphosphate↗
PubMed1990

Effect of temperature on myosin phosphorylation in mouse skeletal muscle.

The effect of muscle contraction on phosphorylatable myosin light chain (P-light chain) phosphate content and isometric twitch tension was examined at 25, 30, and 35 degrees C in intact mouse extensor digitorum longus muscle. Peak tetanic tension was unaffected by temperature, whereas peak unpotentiated isometric twitch tension was inversely proportional to muscle incubation temperature. The extent of phosphate incorporation into P-light chain elicited by a 20-s train of twitches (5/s) was inversely proportional to muscle incubation temperature, whereas the fractional increase in twitch tension (twitch potentiation) elicited by repetitive stimulation was directly proportional to muscle incubation temperature. After the twitch train, the rate of decline of potentiated twitch tension and of P-light chain dephosphorylation was directly proportional to muscle incubation temperature. The net result was that a significant and unique relationship between P-light chain phosphate content and contraction-induced tension potentiation existed at each temperature examined. The slope of the P-light chain phosphate vs. isometric twitch potentiation relationship varied directly as a function of muscle incubation temperature. The observations that the slope of this relationship increases and that unpotentiated twitch tension decreases when muscle incubation temperature is increased support the hypothesis that contraction-induced tension potentiation in intact mammalian skeletal muscle is the result of a sensitization of the contractile element to activation by Ca2+ that is brought about by P-light chain phosphorylation.

Animals↗
PubMed1990

Lymphocyte subset responses to repeated submaximal exercise in men.

The effects of repeated bouts of submaximal cycle ergometry exercise on changes in the percentage of peripheral blood T-lymphocytes, the T-helper/inducer and T-cytotoxic/suppressor subsets, and natural killer (NK) cells were studied in 18 healthy young men who had no history of regular exercise training. Subjects were matched on the basis of maximal O2 uptake and assigned randomly to exercise or control groups, with controls resting quietly during the exercise sessions. The percentage of peripheral blood mononuclear leukocytes that reacted with monoclonal antibodies specific for T-lymphocytes (CD3+ cells), the helper/inducer subset (CD4+ cells) and cytotoxic/suppressor subset (CD8+ cells) of T-lymphocytes, and cells with NK activity (Leu7+ cells) were enumerated by fluorescence-activated flow cytometry for samples obtained immediately before and after exercise on days 1, 3, and 5 of a 5-day exercise regimen. The results of this study were mixed with decreases in the percentage of T-lymphocytes before vs. after exercise on days 1 and 3 (P less than 0.001), a decrease in the percentage of T-helper/inducer cells before vs. after exercise on day 3 (P less than 0.05), no effect of exercise on the percentage of T-cytotoxic/suppressor cells, and a marked increase in the percentage of NK cells after exercise on days 1 (P less than 0.05) and 3 (P less than 0.01). The total number of recovered NK cells in the mononuclear leukocyte fraction of blood also increased significantly after exercise on days 1 (P less than 0.05) and 3 (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗