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Biomedical subjects

K A Edman

Publications and source records attributed to K A Edman.

At least 19 recordsLinked to original sources
PubMed1999

The force bearing capacity of frog muscle fibres during stretch: its relation to sarcomere length and fibre width.

1. Single fibres isolated from the anterior tibialis muscle of Rana temporaria were tetanized (0.9-1.8 C) while a marked ( approximately 1 mm) segment was held at constant length by feedback control. Force enhancement was produced by applying a controlled stretch ramp to the fibre segment during the tetanus plateau, the steady force reached during stretch being used as a measure of the maximum force that the myosin cross-bridges can hold before they detach. 2. The amplitude of force enhancement during stretch did not vary in proportion to the isometric force as the sarcomere length was changed, maximum force enhancement being attained near 2.4 microm sarcomere length compared with 2.0 microm for the isometric force. 3. The influence of fibre width on the force enhancement-sarcomere length relationship was evaluated by normalizing force enhancement to the tetanic (pre-stretch) force in this way allowing for the differences in myofilament overlap at the various lengths. The amplitude of force enhancement (normalized to the tetanic force) increased by approximately 70 % as the relative width of the myofilament lattice was reduced from a nominal value of 1.05 at a sarcomere length of 1.8 microm to 0.85 at a sarcomere length of 2.8 microm. 4. Changes in fibre width equivalent to those produced by altering the sarcomere length were produced by varying the tonicity of the extracellular medium. Force enhancement, normalized to the control isometric force at each tonicity, exhibited a width dependence that agreed well with that described in the previous point. Stretch ramps applied to frog skinned muscle fibres during calcium-induced contracture likewise resulted in a greater force enhancement during stretch after reducing the fibre width by osmotic compression. 5. The results suggest that the strength of binding of the myosin cross-bridges, unlike the isometric force, varies with the lateral distance between the myofilaments.

Animals↗
PubMed1998

Changes in the maximum speed of shortening of frog muscle fibres early in a tetanic contraction and during relaxation.

1. Isotonic shortening velocities at very light loads were examined in single fibres of the anterior tibialis muscle of the frog, Rana temporaria, using load-clamp recording and slack tests (temperature, 1-3 degrees C; initial sarcomere length, 2.25 microns). 2. Shortening velocities at very light loads (force-clamp recording) were found to be higher early in the rise of a tetanic contraction than during the plateau of the contraction. The upper limit of the load at which there was elevated shortening velocity early in the contraction was 1.5-5.4% of the maximum tetanic tension (Fo) depending on the particular fibre. 3. The maximum shortening velocity determined using the slack test method (Vo) was as much as 30% greater early in a contraction than at the tetanic plateau. Vo was elevated above the plateau level up to about 30 ms after the end of the latent period, which is equivalent to the time required for the force in an isometric contraction to rise to about 30% of Fo. Vo is depressed below the plateau value during relaxation at the cessation of stimulation. 4. Stimulation studies show that the cross-bridge model of Huxley (1957) predicts the maximum shortening velocity to be greater early in a contraction, when new actin binding sites are becoming activated and new cross-bridge connections are being formed rapidly, than during steady-state contraction. The elevated shortening velocity in the model is a consequence of new cross-bridges being formed in the pulling configuration, and there being a delay before the newly added bridges are dragged beyond their equilibrium position so they begin to retard shortening. The model also predicts that maximum shortening velocity should be depressed below the plateau level during early relaxation as cross-bridge binding sites are rapidly removed from the active population.

Algorithms↗
PubMed1998

Effects of BAPTA on force and Ca2+ transient during isometric contraction of frog muscle fibers.

The effects of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) on force and intracellular Ca2+ transient were studied during isometric twitches and tetanuses in single frog muscle fibers. BAPTA was added to the bathing solution in its permeant AM form (50 and 100 microM). There was no clear correlation between the changes in force and the changes in Ca2+ transient. Thus during twitch stimulation BAPTA did not suppress the Ca2+ transient until the force had been reduced to <50% of its control value. At the same time, the peak myoplasmic free Ca2+ concentration reached during tetanic stimulation was markedly increased, whereas the force was slightly reduced by BAPTA. The effects of BAPTA were not duplicated by using another Ca2+ chelator, EGTA, indicating that BAPTA may act differently as a Ca2+ chelator. Stiffness measurements suggest that the decrease in mechanical performance in the presence of BAPTA is attributable to a reduced number of active cross bridges. The results could mean that BAPTA, under the conditions used, inhibits the binding of Ca2+ to troponin C resulting in a reduced state of activation of the contractile system.

Animals↗
PubMed1997

The biphasic force-velocity relationship in frog muscle fibres and its evaluation in terms of cross-bridge function.

1. The relationship between force and velocity of shortening was studied during fused tetani of single fibres isolated from the anterior tibialis muscle of Rana temporaria (1.5-3.3 degrees C; sarcomere length, 2.20 microns). Stiffness was measured as the change in force that occurred in response to a 4 kHz length oscillation of the fibre. 2. The results confirmed the existence of two distinct curvatures of the force-velocity relationship located on either side of a breakpoint in the high-force, low-velocity range. Reduction of the isometric force (P0) to 83.4 +/- 1.7% (mean +/- S.E.M., n = 5) of the control value by dantrolene did not affect the relative shape of the force-velocity relationship. The breakpoint between the two curvatures was located at 75.9 +/- 0.9% of P0 and 11.4 +/- 0.6% of maximum velocity of shortening (Vmax) in control Ringer solution and at 75.6 +/- 0.7% of P0 and 12.2 +/- 0.7% of Vmax in the presence of dantrolene. These results provide evidence that the transition between the two curvatures of the force-velocity relationship is primarily related to the speed of shortening, not to the actual force within the fibre. 3. The instantaneous stiffness varied with the speed of shortening forming a biphasic relationship with a breakpoint near 0.15 Vmax and 0.8 P0, respectively. The force/stiffness ratio (probably reflecting the average force per cross-bridge), increased with force during shortening. The increase of the force/stiffness ratio with force was less steep at forces exceeding 0.8 P0 than below this point. 4. A four-state cross-bridge model (described in the Appendix) was used to evaluate the experimental results. The model reproduces with great precision the characteristic features of the force-stiffness-velocity relationships recorded in intact muscle fibres.

Animals↗
PubMed1996

Strain of passive elements during force enhancement by stretch in frog muscle fibres.

1. The force enhancement during and after stretch (0.15 micron per sarcomere) was studied during fused tetani of single fibres isolated from the anterior tibialis muscle of Rana temporaria (0.5-3.6 degrees C; sarcomere length, 2.05-2.65 microns). Changes in length were recorded simultaneously from the fibre as a whole (puller movement) and from marked segments (approximately 0.5 mm in length) of the same fibre. 2. The residual force enhancement after stretch (recorded at the end of a long tetanus) was found to be linearly related to the slow component of tension rise during the stretch ramp. 3. The fibres were released to shorten against a very small load at different times after stretch (load clamp). The shortening records derived after a preceding stretch exhibited a larger and steeper initial transient than that recorded in an isometric tetanus without stretch. The excess length change (LS; nanometres per half-sarcomere) recorded during the initial transient increased with the amplitude of stretch and was linearly related to the force enhancement produced by the stretch (FE; % of maximum tetanic tension) according to the following regression: LS = 0.200 FE + 8.65 (P < 0.001). The length changes recorded from the whole fibre agreed well with measurements from individual segments. 4. Slack-test measurements confirmed the existence of a large initial transient phase when the fibre was released to shorten after a preceding stretch. The excess length change determined from the slack tests agreed closely with the values derived from load-clamp recordings. 5. The results support the view that stretching a muscle fibre during tetanus leads to strain of elastic elements and, presumably, to variation of filament overlap due to non-uniform distribution of the length change within the fibre volume. Regions with greater filament overlap are likely to generate the long-lasting extra force referred to as 'residual force enhancement after stretch'. The elastic elements recruited during stretch can be presumed to play an essential part in this process by supporting regions in which the filament overlap has been reduced during the stretch ramp. Recoil of these elastic elements is responsible for the excess length change that is recorded during the initial transient after release as described under point 3.

Animals↗
PubMed1996

Fatigue vs. shortening-induced deactivation in striated muscle.

Fatigue and shortening-induced deactivation, two conditions that both lead to reversible depression of the mechanical performance of striated muscle are briefly reviewed. Fatigue. Isolated fibres from frog skeletal muscle (1-3 degrees C) that are stimulated to produce a 1 s fused tetanus at 15 s intervals are brought into a state of myofibrillar fatigue, (tetanic force reduced to 70-75% of the control) that is attributable to reduced performance of the myofibrils with no significant change in activation of the contractile system. A more intense stimulation programme (a single stimulus applied at 1-2 s intervals) reduces the tetanic force below 70% of the rested-state level. Under these conditions, failure of activation becomes increasingly important as a cause of the force decline. Deficient inward spread of activation is likely to account for at least part of the force decline after a period of intense fatiguing stimulation. Shortening-induced deactivation. Striated muscle that is allowed to shorten during activity loses some of its capacity to produce force, full restoration of the contractile strength being attained 1-2 s after the shortening phase. The depressant effect of shortening is demonstrable in skinned preparations as well as in intact muscle fibres and the magnitude of the effect is dependent on the state of activation of the muscle fibre when the movement occurs. The experimental evidence supports the view that sliding of the thick and thin filaments during activity reduces the affinity for calcium at the regulatory sites on the thin filament, leading to a transitory deactivation of the contractile system.

Animals↗
PubMed1996

The relationship between the intracellular Ca2+ transient and the isometric twitch force in frog muscle fibres.

The calcium-sensitive fluorescent indicator fluo-3 was used to monitor the intracellular free calcium concentration ([Ca2+]i) during isometric twitches in twenty-nine single muscle fibres from the anterior tibialis muscle of Rana temporaria (sarcomere length, 2.2 microns; 2-4 degrees C). The transient change in [Ca2+]i in response to a single stimulus was very brief. The time to peak and the duration of the Ca2+ signal, measured at 50% of the peak amplitude, were 8.3 +/- 0.2 and 22.1 +/- 1.4 ms (mean +/- S.E.M., n = 29), respectively. The mean peak amplitude of the Ca2+ transient was 3.2 +/- 0.1 microM, ranging from 2.46 to 3.92 microM among the different fibres. The isometric force started to rise 2.5 ms before [Ca2+]i reached its maximum value. When peak twitch force was attained, [Ca2+]i had already declined to approximately 10% of its maximum value. The peak force produced during a twitch was closely related to the decay phase of the Ca2+ transient, a slower decay of [Ca2+]i being associated with a greater amplitude of the twitch. The amplitude and duration of the Ca2+ transient varied in a systematic way relative to one another in different fibres, in that a greater amplitude was associated with a more rapid decay of the Ca2+ transient. NO3- and Zn2+ added to the external medium greatly enhanced the peak twitch force without markedly affecting the amplitude of the Ca2+ transient. However, both agents delayed the decay of [Ca2+]i. It is concluded that the decay phase of the Ca2+ transient is a more important determinant of the mechanical response during an isometric twitch than is the peak amplitude of the transient.

Aniline Compounds↗
PubMed1995

Myofibrillar fatigue versus failure of activation.

Two principal mechanisms underlying fatigue of isolated muscle fibers are described: failure of activation of the contractile system and reduced performance of the myofibrils due to altered kinetics of crossbridge function. The relative importance of these two mechanisms during development of fatigue is discussed.

Animals↗
PubMed1995

The effects of 2,3-butanedione monoxime (BDM) on the force-velocity relation in single muscle fibres of the frog.

The effects of 2,3-butanedione monoxime (BDM) on the force-velocity relation were studied in single fibres from the anterior tibialis muscle of Rana temporaria (2.2 microns sarcomere length, temperature 1.9-2.4 degrees C). BDM (1.0 and 1.8 mM) suppressed the maximum tetanic force (P0) and the maximum speed of shortening (Vmax), and increased the main curvature of the force-velocity relation. The biphasic shape of the force-velocity curve was maintained well in the presence of BDM, but the interrelation between the two portions of the force-velocity relation was significantly changed. Caffeine (0.5 mM) added in the presence of BDM increased the initial rate of rise of force during twitch and tetanus, increased the twitch amplitude, but did not affect the maximum tetanic force. The latter finding suggests that the contractile system was fully activated during tetanus in the presence of BDM. The results support the view that BDM affects the cross-bridge function by exerting a direct action upon the contractile apparatus. The decrease in tetanic force and the change of the force-velocity relation induced by BDM may be interpreted to show that a larger fraction of the attached cross-bridges is in a state of low force production under the influence of BDM. This view is further supported by the observation that the instantaneous stiffness of the muscle fibre is reduced proportionally less by BDM than the tetanic force.

Animals↗
PubMed1994

Variation in myoplasmic Ca2+ concentration during contraction and relaxation studied by the indicator fluo-3 in frog muscle fibres.

1. The fluorescent dye fluo-3, in its permeant acetoxymethyl form, was used to monitor calcium transients during twitch and tetanus of single fibres isolated from the anterior tibialis muscle of Rana temporaria (2-5 degrees C). 2. Fluo-3 was loaded into the muscle fibre by diffusion. Under the experimental conditions used, approximately 45% of maximal fluorescence was reached during a 1 s fused isometric tetanus. Fluo-3 had no detectable effect on the mechanical response of the fibre. 3. The free calcium concentration in the myoplasm, [Ca2+]i, and its variation with time, was calculated from the fluorescence signal by accounting for the on- and off-rate constants for the binding of calcium to the dye. The time course of the calcium transient during twitch and tetanus determined in this way agreed well with previous measurements based on fast-reacting calcium-sensitive dyes. 4. [Ca2+]i declined steeply during the initial phase of force relaxation in both twitch and tetanus, but exhibited a secondary rise that closely coincided with the pseudoexponential fall of tension after the shoulder in the tetanus myogram. The rate of decay of [Ca2+]i during relaxation and the rate of decline of force both became progressively reduced by repetitive stimulation. 5. Stretch and shortening ramps performed during the plateau of an isometric tetanus had no detectable effect upon the calcium transient during the movement. By contrast, shortening and stretch imposed during the linear phase of relaxation both led to an increase of [Ca2+]i and to a steepening of the relaxation phase. 6. The results strongly suggest that the non-uniform length changes that are known to occur along a muscle fibre during relaxation enhance the release of calcium from the contractile system. The calcium mobilized in this way probably accounts for the transitory increase of [Ca2+]i that is observed during the latter part of force relaxation.

Aniline Compounds↗
PubMed1994

Force-velocity relation for frog muscle fibres: effects of moderate fatigue and of intracellular acidification.

1. Intact frog single fibres were investigated under control conditions (1 s tetanus every 2, 3 or 5 min) and during moderate fatigue (interval between tetani 15 or 30 s). 2. Fatigue reduced isometric force (P0) by 25.8 +/- 1.6% (S.E.M.; n = 13) and depressed the maximum velocity of shortening (Vmax) by 10.2 +/- 2.2% (n = 13). The force-velocity relation became less curved, a/P0* (see Methods) being increased by 29.5 +/- 8.8% (n = 13). Thus, power was less affected than isometric force or Vmax. 3. The velocity of unloaded shortening (V0), from slack test measurements, was reduced proportionally more than Vmax during fatigue. Under control conditions V0 was larger than Vmax, but during fatigue their values were not significantly different. 4. Stiffness during shortening was reduced during fatigue indicating fewer attached cross-bridges in fatigue. Force was reduced more than stiffness indicating that, on average, there is less force per attached cross-bridge. 5. The force-lengthening velocity relation showed that the ability to resist forces greater than isometric was well preserved in fatigue. 6. Compared with fatigue, intracellular acidification with CO2 produced a smaller reduction in isometric force. However, reduction in Vmax was not significantly different from that in fatigue. These results are consistent with both inorganic phosphate and H+ increasing in fatigue, but only H+ increasing during acidification, and isometric force being reduced by both, Vmax being sensitive only to H+.

Acids↗
PubMed1993

Mechanism underlying double-hyperbolic force-velocity relation in vertebrate skeletal muscle.

The force-velocity relation of frog striated muscle exhibits two distinct curvatures located on either side of a breakpoint that occurs near 80% of maximum isometric force (Po) where the shortening velocity is approximately 1/10 of Vmax. The present experiments have been performed to further elucidate the high-force deviation of the force-velocity curve in frog single muscle fibres. The biphasic shape of the force-velocity curve appears at the same relative values of Po and Vmax also after depressing the isometric force to 80% of the control value by dantrolene, a substance known to reduce the release of activator calcium from the sarcoplasmic reticulum. This finding suggests that the breakpoint of the force-velocity curve is not related to the force level per se but rather to the speed of shortening of the contractile system. Thus as the speed of shortening goes below 1/10 of Vmax, the performance of the myofilament system is changed such that less force and less motion are produced than expected from the main part of the force-velocity curve. In a series of experiments active force and fibre stiffness were simultaneously recorded while the fibre shortened at various speeds during tetanus. Stiffness was measured as the change in force that occurred in response to a 4 kHz sinusoidal length oscillation of the fibre. A plotting of stiffness against force recorded under these conditions provides a biphasic relationship with a distinct transition between the two phases near 80% of Po, i.e. at the same relative force at which the breakpoint occurs in the force-velocity curve. Above 0.8 Po stiffness increases more steeply with force than below this point. This means that while more crossbridges than expected attach to the thin filaments when the load is raised above 0.8 Po, the force output and the speed of shortening become lower than predicted from measurements at low and intermediate loads. The results suggest that the kinetics of crossbridge function is changed as the speed of filament sliding is reduced below a critical level, 1/10 of Vmax. Beyond this point a greater portion of myosin crossbridges would seem to accumulate in a state where less force is being produced. Data are also presented to further elucidate the force-velocity relation at negative loads. In these experiments the passive tension at long sarcomere lengths has been utilized to produce a longitudinal compressive force on the sarcomeres during unloaded shortening (force-clamp recording).(ABSTRACT TRUNCATED AT 400 WORDS)

Actin Cytoskeleton↗
PubMed1993

Depression of tetanic force induced by loaded shortening of frog muscle fibres.

1. Single fibres isolated from the anterior tibialis muscle of Rana temporaria were allowed to shorten against a high load during a 2.5-4.0 s fused tetanus (1-3 degrees C) and the maximum force produced at the short length was compared with that recorded during a fixed-end tetanus at the same overall fibre length. Changes in length of marked, consecutive segments (ca 0.5 mm in length) along the fibre were measured throughout the tetanus using a photoelectric recording system. 2. Loaded shortening (load ca 3/4 of maximum tetanic force) starting from approximately 2.55 microns sarcomere length and ending near slack fibre length depressed the tetanic force by 13 +/- 2% (mean +/- S.E.M., n = 10) and caused a marked redistribution of sarcomere length along the fibre. Unloaded shortening over the same range caused no force deficit and did not lead to increased dispersion of sarcomere length. 3. Loaded shortening below slack length produced less force depression and less non-uniformity of sarcomere length than did a corresponding intervention above slack length. 4. The force deficit after loaded shortening, both above and below slack fibre length, was positively correlated (P < 0.005) to the coefficient of variation of the sarcomere length along the fibre. 5. The decrease in active force after loaded shortening, and its relation to increased dispersion of sarcomere length along the fibre, could be simulated closely by a computer model in which the muscle fibre was assumed to consist of eleven discrete segments acting in series with a passive elastic element. 6. Experiments were performed in which the length of an individual segment of the intact muscle fibre was strictly controlled throughout a tetanus. Loaded shortening of such a 'length-clamped' segment caused no force depression during the subsequent isometric phase either above or below slack fibre length. 7. The results suggest strongly that force depression after loaded shortening of a single muscle fibre is attributable to non-uniform sarcomere behaviour along the fibre. The experimental evidence supports the view that: (i) the myosin cross-bridges act as independent force generators; and (ii) their steady-state performance during a tetanus is unaffected by the preceding contractile activity.

Animals↗
PubMed1992

Myofibrillar fatigue versus failure of activation during repetitive stimulation of frog muscle fibres.

1. Single fibres isolated from the anterior tibialis muscle of Rana temporaria (temperature, 2-5 degrees C; sarcomere length, 2.10 microns) were fatigued using two separate protocols that led to different degrees of depression of tetanic force. Under control conditions the fibre was stimulated to produce a 1 s fused isometric tetanus at 300 s intervals. A moderate degree of fatigue (tetanic force reduced to 70-80% of the control value) was produced by decreasing the intervals between tetani to 15 s ('fatiguing protocol 1'). A more pronounced depression of tetanic force (to 40-50% of the control value) was produced by evoking a single twitch at 1-2 s intervals ('fatiguing protocol 2'). 2. Fatiguing protocol 1 reduced the contracture response to submaximal and supramaximal concentrations of caffeine (3-15 mM) in proportion to the decrease in tetanic force. These results support the view that fatiguing stimulation according to protocol 1 leads to a true 'myofibrillar fatigue' with no failure of activation of the muscle fibre. 3. Fatiguing protocol 2 reduced the amplitudes of isometric twitch and tetanus to below 10 and 50% of the control values, respectively. By contrast, the maximal contracture response to caffeine (15 mM) was depressed by merely 2-3% of its prefatigue value. 4. Force and instantaneous fibre stiffness were recorded simultaneously during twitch and tetanus as fatigue was induced by protocol 2. During the initial part of fatigue (tetanic force reduced by 25% of control) stiffness was reduced by merely 9% in accordance with previous measurements during fatigue induced by protocol 1. However, with further depression of twitch and tetanus by protocol 2 there was a marked reduction of fibre stiffness. These results, together with the findings reported under point 3, strongly suggest that at an advanced state of fatigue induced by protocol 2 the decrease in active force is largely due to failure of activation of the contractile system. 5. Muscle fibres were quickly frozen for electron microscopical examination after shortening below slack length (to approximately 1.6 microns sarcomere spacing) during tetanic stimulation. In non-fatigued fibres, and in fibres fatigued according to protocol 1, the myofibrils exhibited a straight appearance throughout the preparation suggesting that the entire volume of the fibre was properly activated. In fibres fatigued by protocol 2, on the other hand, only the most peripheral layers of myofibrils remained straight after shortening, whereas the centre of the fibre showed marked waviness indicating failure of the inward spread of activation in this case.

Animals↗
PubMed1990

Changes in force and stiffness induced by fatigue and intracellular acidification in frog muscle fibres.

1. Changes in force and stiffness were recorded simultaneously during 1 s isometric (fixed ends) tetani of single fibres isolated from the anterior tibialis muscle of Rana temporaria (temperature 1-3 degrees C; sarcomere length, 2.10 micron). Stiffness was measured as the change in force that occurred in response to a 4 kHz sinusoidal length oscillation of the fibre. Some experiments were performed in which stiffness was determined from a fast (0.2 ms) length step that was applied to a 'tendon-free' segment of the muscle fibre during the tetanus plateau. 2. A moderate degree of fatigue was produced by decreasing the time between tetani from 300 s (control) to 15 s. By this treatment the maximum tetanic force (Ftet) was reversibly reduced to 70-75% of the control value. Maximum tetanic stiffness (Stet) was related to Ftet according to the following regression (both variables expressed as percentage of their control values): Stet = 0.369 Ftet + 62.91 (correlation coefficient, 0.95; P less than 0.001). A 25% decrease in isometric force during fatigue was thus associated with merely 9% reduction of fibre stiffness. 3. Whereas the rate of rise of force during tetanus was markedly reduced by fatiguing stimulation, the rate of rise of stiffness was only slightly affected. 4. Intracellular acidification (produced by raised extracellular CO2 concentration) largely reproduced the contractile changes observed during fatigue. However, for a given decrease in tetanic force there was a smaller reduction in fibre stiffness during acidosis than during fatigue. 5. Caffeine (0.5 mM) added to the fibre after development of fatigue and intracellular acidosis greatly potentiated the isometric twitch but did not affect maximum tetanic force. This finding provides evidence that the contractile system was fully activated during the tetanus plateau both in the fatigued state and during acidosis. 6. The results suggest that the decrease in contractile strength after frequent tetanization (intervals between tetani, 15 s) is attributable to altered kinetics of cross-bridge function leading to reduced number of active cross-bridges and, most significantly, to reduced force output of the individual bridge. The possible role of increased intracellular H+ concentration in the development of muscle fatigue is discussed.

Animals↗
PubMed1989

Effects of amrinone on twitch, tetanus and shortening kinetics in mammalian skeletal muscle.

The contractile effects of amrinone were studied on twitch and tetanus responses of mouse lumbrical muscles. Amrinone (1.1 mM) increased the maximum force level during the tetanus, reduced the rate of rise of force during the onset of tetanus and prolonged the time from the last stimulus to half-relaxation. The rate of redevelopment of force after a release during the tetanus plateau was likewise reduced. Amrinone (greater than or equal to 0.5 mM) increased the time to peak twitch force and the time to half-relaxation during the twitch. The peak twitch force was not significantly changed. The force-velocity relation was markedly affected by amrinone: there was a decrease in maximum velocity of shortening, an increase in maximum isometric force and a decrease in curvature of the force-velocity relation. The results suggest that amrinone modulates the kinetic properties of the myosin cross-bridges by exerting a specific effect upon the myofilament system. The latter effects are mainly responsible for the contractile changes produced by amrinone in mouse skeletal muscle. Amrinone appears to have little effect on the metabolism of activator calcium in this particular preparation.

Amrinone↗
PubMed1989

Effects of fatigue and reduced intracellular pH on segment dynamics in 'isometric' relaxation of frog muscle fibres.

1. Longitudinal movements of marked segments of single fibres from the anterior tibialis muscle were recorded during tetanus and relaxation under isometric (fixed-end) conditions. 2. During relaxation, shortening and lengthening of different segments occurred simultaneously, starting at about the same time as the end of the linear fall of force (shoulder on the force record). 3. Variations in intracellular pH, measured with pH-sensitive microelectrodes, along the length of fibres were not statistically significant, and are unlikely to be responsible for the non-uniform behaviour of different segments. 4. As expected from earlier studies, both fatigue (produced by increasing tetanus duration or decreasing the time between tetani) and intracellular acidification (produced by raised extracellular CO2), reduced the tetanus force and prolonged the linear phase of force decline in relaxation. Each treatment delayed the start and markedly reduced the amount of segment movement in relaxation. 5. Fatigue and intracellular acidification have a smaller effect on force during stretching than on force produced under isometric conditions. This may contribute to making the segments behave in a more uniform way during relaxation under these conditions. 6. Changes in the Ca2+ uptake mechanisms are also discussed as possible causes for the changes in segment behaviour in relaxation.

Animals↗