Biomedical subjects

R W Grange

Publications and source records attributed to R W Grange.

At least 19 recordsLinked to original sources

PubMed1999

Role for alpha-dystrobrevin in the pathogenesis of dystrophin-dependent muscular dystrophies.

A dystrophin-containing glycoprotein complex (DGC) links the basal lamina surrounding each muscle fibre to the fibre's cytoskeleton, providing both structural support and a scaffold for signalling molecules. Mutations in genes encoding several DGC components disrupt the complex and lead to muscular dystrophy. Here we show that mice deficient in alpha-dystrobrevin, a cytoplasmic protein of the DGC, exhibit skeletal and cardiac myopathies. Analysis of double and triple mutants indicates that alpha-dystrobrevin acts largely through the DGC. Structural components of the DGC are retained in the absence of alpha-dystrobrevin, but a DGC-associated signalling protein, nitric oxide synthase, is displaced from the membrane and nitric-oxide-mediated signalling is impaired. These results indicate that both signalling and structural functions of the DGC are required for muscle stability, and implicate alpha-dystrobrevin in the former.

Animals↗

PubMed1998

Mice without myoglobin.

Myoglobin, an intracellular haemoprotein expressed in the heart and oxidative skeletal myofibres of vertebrates, binds molecular oxygen and may facilitate oxygen transport from erythrocytes to mitochondria, thereby maintaining cellular respiration during periods of high physiological demand. Here we show, however, that mice without myoglobin, generated by gene-knockout technology, are fertile and exhibit normal exercise capacity and a normal ventilatory response to low oxygen levels (hypoxia). Heart and soleus muscles from these animals are depigmented, but function normally in standard assays of muscle performance in vitro across a range of work conditions and oxygen availability. These data show that myoglobin is not required to meet the metabolic requirements of pregnancy or exercise in a terrestrial mammal, and raise new questions about oxygen transport and metabolic regulation in working muscles.

Animals↗

PubMed1998

Skeletal muscle contractions stimulate cGMP formation and attenuate vascular smooth muscle myosin phosphorylation via nitric oxide.

Nitric oxide generated by neuronal nitric oxide synthase in contracting skeletal muscle fibers may regulate vascular relaxation via a cGMP-mediated pathway. Neuronal nitric oxide synthase content is greatly reduced in skeletal muscles from mdx mice. cGMP formation increased in contracting extensor digitorum longus muscles in vitro from C57 control, but not mdx mice. The increase in cGMP content was abolished with NG-nitro-L-arginine. Sodium nitroprusside treatment increased cGMP levels in muscles from both C57 and mdx mice. Skeletal muscle contractions also inhibited phenylephrine-induced phosphorylation of smooth muscle myosin regulatory light chain. Arteriolar dilation was attenuated in contracting muscles from mdx but not C57 mice. NO generated in contracting skeletal muscle may contribute to vasodilation in response to exercise.

Animals↗

PubMed1998

Potentiation of in vitro concentric work in mouse fast muscle.

Phosphorylation of myosin regulatory light chain (R-LC) is associated with potentiated work and power during twitch afterloaded contractions in mouse extensor digitorum longus muscle [R. W. Grange, C. R. Cory, R. Vandenboom, and M. E. Houston. Am. J. Physiol. 269 (Cell Physiol. 38): C713-C724, 1995]. We now describe the association between R-LC phosphorylation and potentiated concentric work when the extensor digitorum longus muscle is rhythmically shortened and lengthened to simulate contractions in vivo. Work output (at 25 degrees C) was characterized at sine frequencies of 3, 5, 7, 10, and 15 Hz at excursions of 0.6, 1.2, and 1.6 mm (approximately 5, 9, and 13% optimal muscle length) at a low level of R-LC phosphorylation. Muscles stimulated during the sine function with a single twitch at specific times before or after the longest muscle length yielded maximal concentric work near the longest muscle length at a sine frequency of 7 Hz (e.g., excursion approximately 9% optimal muscle length = 1.6 J/kg). Power increased linearly between sine frequencies of 3 and 15 Hz at all excursions (maximum approximately 29 W). After a 5-Hz 20-s conditioning stimulus and coincident with a 3.7-fold increase in R-LC phosphate content (e.g., from 0.19 to 0.70 mol phosphate/mol R-LC), work at the three excursions and a sine frequency of 7 Hz was potentiated a mean of 25, 44, and 50% (P < 0.05), respectively. The potentiated work during rhythmic contractions is consistent with enhanced interaction between actin and myosin in the force-generating states. On the basis of observations in skinned skeletal muscle fibers (H. L. Sweeney and J. T. Stull. Proc. Natl. Acad. Sci. USA 87:414-418, 1990), this enhancement could result from increased phosphate incorporation by the myosin R-LC. Under the assumption that the predominant effect of the conditioning stimulus was to increase R-LC phosphate content, our data suggest that a similar mechanism may be evident in intact muscle.

Animals↗

PubMed1997

Adenovirus-mediated transfer of the smooth muscle cell calponin gene inhibits proliferation of smooth muscle cells and fibroblasts.

Smooth muscle cell calponin (h1 or basic isoform) is an actin-binding protein that inhibits actomyosin MgATPase activity and is abundantly expressed in differentiated smooth muscle. Western blots showed bovine tracheal (BT) smooth muscle cells in culture expressed only 2 +/- 1% (n = 8) of the amount of calponin in tissues, while NIH-3T3 fibroblasts expressed none. We tested the hypothesis that introduction of calponin to cultured BT and 3T3 cells would inhibit cytoskeletal activities associated with cell proliferation. To achieve high-efficiency expression, an adenovirus encoding the CMV-calponin construct (Adv-CaP) was generated by homologous recombination in 293 cells. With greater than 90% of BT and 3T3 cells infected with Adv-CaP, calponin expression (32 and 11 microg/mg total protein, respectively) was similar to that in smooth muscle tissues (51 microg/mg). Cells were infected with Adv-CaP for 48 h, replated at low density and proliferation rates were assessed by cell density and [3H]thymidine incorporation. Cell growth and DNA synthesis by Adv-CaP-infected cells were inhibited to one-third control values for both BT and 3T3 cells. Expressed calponin was localized primarily on stress fibers in both cell types. Calponin may act at the cytoskeletal level to retard signaling pathways that normally lead to tight coupling between cell shape and DNA synthesis.

3T3 Cells↗

PubMed1997

Pleiotropic effects of a disrupted K+ channel gene: reduced body weight, impaired motor skill and muscle contraction, but no seizures.

To investigate the roles of K+ channels in the regulation and fine-tuning of cellular excitability, we generated a mutant mouse carrying a disrupted gene for the fast activating, voltage-gated K+ channel Kv3.1. Kv3.1-/- mice are viable and fertile but have significantly reduced body weights compared with their Kv3.1+/- littermates. Wild-type, heterozygous, and homozygous Kv3.1 channel-deficient mice exhibit similar spontaneous locomotor and exploratory activity. In a test for coordinated motor skill, however, homozygous Kv3.1-/- mice perform significantly worse than their heterozygous Kv3.1+/- or wild-type littermates. Both fast and slow skeletal muscles of Kv3.1-/- mice are slower to reach peak force and to relax after contraction, consequently leading to tetanic responses at lower stimulation frequencies. Both mutant muscles generate significantly smaller contractile forces during a single twitch and during tetanic conditions. Although Kv3.1-/- mutants exhibit a normal auditory frequency range, they show significant differences in their acoustic startle responses. Contrary to expectation, homozygous Kv3.1-/- mice do not have increased spontaneous seizure activity.

Age Factors↗

PubMed1997

Stiffness of the inferior oblique neurofibrovascular bundle.

PURPOSE: To assess the mechanical ability of the inferior oblique neurofibrovascular bundle (NFVB) to act as an ancillary origin for the inferior oblique muscle after anterior transposition. METHODS: Stress-strain relations and Young's modulus of elasticity, a measure of tissue stiffness, were determined for the NFVB in vitro, in situ, and in vivo in dynamic and static conditions. For comparison, similar studies were performed in vitro on the superior oblique tendon (SOT). RESULTS: Young's moduli for NFVB in situ (6.3 MPa [megapascals]) and in vivo (11.8 MPa) were approximately 2 and 4 times greater (P < 0.05), respectively, than those of isolated NFVB in vitro at 5% to 10% dynamic strain (3 MPa). In dynamic conditions, Young's moduli in vitro for the NFVB and the SOT were similar. CONCLUSIONS: The NFVB is a biomaterial that has stiffness properties similar to the SOT. Within the range of forces typical of normal eye movements (79 to 393 mN), the NFVB alone can tolerate forces of 98 mN at 0% to 10% strain and 393 mN at 15% to 20% strain, based on dynamic in vitro analysis. The greater measured stiffness in situ and in vivo suggest that the NFVB in the intact orbit potentially has a resting strain of 15% to 20%, and additional tissues in parallel with the NFVB also contribute to total stiffness. These data support the hypothesis that the NFVB, acting alone or in concert with adjacent orbital tissues, may form an ancillary origin for the inferior oblique muscle after anterior transposition.

Connective Tissue↗

PubMed1995

Myosin phosphorylation enhances rate of force development in fast-twitch skeletal muscle.

Skeletal muscle force output is regulated through Ca(2+)-mediated alterations of the rate at which cross bridges make the transition from non-force-generating to force-generating states, defined by the rate constant fapp. In skinned-fiber models, phosphate incorporation by the regulatory light chain (R-LC) subunits of myosin increases fapp independent of Ca2+, thus increasing the Ca2+ sensitivity for the rate and extent of steady-state force development. The goal of this study was to determine whether phosphate incorporation by the R-LC subunits of skeletal muscle is related to the maximal rate of isometric force development (+dF/dtmax) in intact muscle. Changes in myosin phosphate content and contractile performance were analyzed at selected times after the application of a 5-Hz 20-s conditioning stimulus (CS) employed specifically to elevate R-LC phosphate content in mouse extensor digitorum longus at 25 degrees C. R-LC phosphate content (in mol phosphate/mol R-LC) increased from 0.13 +/- 0.04 at rest to 0.68 +/- 0.02 20 s after the CS and by 360 s after the CS R-LC phosphate content had decayed to 0.37 +/- 0.06. Values obtained for twitch and tetanic +dF/dtmax after the CS were strongly correlated to R-LC phosphate content (r = 0.97 and 0.96, respectively), suggesting that phosphate incorporation by skeletal myosin R-LC contributes to an enhanced rate of isometric force development in fast-twitch skeletal muscle.

Animals↗

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↗

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↗

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

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↗

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↗