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Biomedical subjects

K A Edman

Publications and source records attributed to K A Edman.

At least 55 records · Page 3Linked to original sources
PubMed1981

Effects of fatigue and altered pH on isometric force and velocity of shortening at zero load in frog muscle fibres.

temporaria (0.9-2.5degrees C) were stimulated to produce a 1 s isometric tetanus at regular intervals until constant mechanical responses were attained. Various degrees of force depression ("fatigue") were produced by decreasing the contraction interval from 30 or 15 min (control to 120, 60, 30 and 15s, respectively. In this was the steady-state tetanic force could be reversibly reduced to approximately 70% of the control value. The velocity of shortening at zero load, V0, was determined at each level of fatigue using an approach for direct measurement of V0. V0 was not significantly affected as long as the decrease in force was less than 10%. With further reduction of the isometric tension there was a progressive decline of V0 according to the following empirical relationship between percentage depression of force (delta P0) and maximum speed (delta V0) of shortening: delta V0 = 0.006 delta P02.48- 1.0 (correlation coefficient, 0.86). Cine photographic recording of nylon markers on the fibre surface provided evidence that fatigue developed uniformly along the fibre with no sign of failure of excitation in any segment. The change in mechanical performance during fatigue could be reproduced inthe non-fatigued fibre by reducing the pH of the external medium within the range 8.0-6.6 using a bicarbonate-CO2 buffer. A decrease in pH thus reduced both the rate of rise and the total amplitude of isometric force and prolonged the relaxation phase. Furthermore, there was a drop in V0 that was related to the force decline in approximately the same way as observed during fatigue. The results support the idea the fatigue involves both a reduced state of activation of the contractile system and a specific (activation independent) inhibition of crossbridge turnover. Increased intracellular H+ concentration is likely to contribute to the development of both these effects during fatigue.

Animals↗
PubMed1981

Critical sarcomere extension required to recruit a decaying component of extra force during stretch in tetanic contractions of frog skeletal muscle fibers.

29 single frog skeletal muscle fibers were stretched during fused tetanic contractions. The force increase during stretch exhibited a breakpoint at a critical length change (average: 16.6 nm per one-half sarcomere) that was independent of velocity of stretch and of sarcomere length between 1.8 and 2.8 microns. After stretch there was an early decaying force component with a force-extension curve similar to that during stretch, which disappeared over approximately 2 s. This component was removed by a small, quick release, leaving a longer-lasting component. The critical amplitude of release required to produce this result was found by clamping the fiber to a load at which there was zero velocity of shortening. This amplitude increased with time up to the angle in the force record during stretch, was constant for the remainder of the stretch, and decreased with time after the end of stretch; it was consistently less than the critical amplitude of stretch required to reach the breakpoint of force enhancement during stretch but was also independent of sarcomere length. The force drop accompanying the critical release showed a small increase up to an optimum magnitude at 2.4--2.7 microns sarcomere length, with a decrease at longer lengths.

Animals↗
PubMed1980

Depression of mechanical performance by active shortening during twitch and tetanus of vertebrate muscle fibres.

Shortening during activity of frog single muscle fibres caused a graded depression of the contractile force that persisted for 800-900 ms during a partially fused or completely fused tetanus. The depression of force was not associated with a change of the shortening velocity at zero load. Passive shortening performed just before stimulation had no effect on the subsequent course of contraction. The decrease in isometric force produced by shortening was not significantly affected by a stretch applied immediately before or after the shortening was not significantly affected by a stretch applied immediately before or after the shortening phase. For a given amount of shortening the depressant effect during a fused tetanus was 8-28% of that produced during a twitch. The effect was substantially reduced, both during twitch and tetanus, in the presence of 0.5 mM caffeine. The length dependence of the movement effect was studied between 1.7 and 2.9 micrometer sarcomere spacing. Maximum depression of force (in per cent of the control at each length) was obtained at 2.1-2.2 micrometer sarcomere length, the effect being steadily reduced at shorter and more extended lengths. The Q10 of the depressant effect was 0.95 +/- 0.16 (S.D.). The features of the movement effect are consistent with a true deactivation of the contractile system as would occur if shortening reduced the binding of activator calcium to the regulatory proteins of the myofilaments.

Animals↗
PubMed1979

Effects of 4-aminopyridine on the excitation-contraction coupling in frog and rat skeletal muscle.

The effects of 4-aminopyridine (4-AP) were studied on isolated single muscle fibres of the frog and toe muscles of the rat. In both muscle preparations, 4-AP potentiated the twitch amplitude without significantly affecting the tetanus response. There was an increase of the time to peak tension and, in frog muscle, an increased time to half relaxation. 4-AP produced no change of the resting membrane potential. The rate of decay and, hence, the total duration of the action potential were markedly prolonged. 4-AP did not induce contractures by itself nor did it affect the contracture induced by caffeine. The mechanical threshold was determined by measuring the contracture response to various degrees of depolarization by potassium. This threshold was not affected by 4-AP. Twitch potentiation by 4-AP was independent of the extracellular calcium concentration. It is concluded that 4-AP potentiates the twitch response by increasing the release of activator calcium into the myofibrillar space by prolongation of the action potential. In addition, there may be a more direct inhibitory action of 4-AP on the calcium re-uptake by the sarcoplasmic reticulum in frog muscle.

Action Potentials↗
PubMed1979

The velocity of unloaded shortening and its relation to sarcomere length and isometric force in vertebrate muscle fibres.

1. The velocity of shortening at zero load was studied during fused tetanic contractions and single twitches in isolated skeletal muscle fibres of Rana temporaria. 2. The technique used for determination of the speed of unloaded shortening consisted of a series of quick releases of different amplitudes applied at a given instant during activity. The time, delta t, needed for the fibre to take up the slack was plotted against the amplitude of release, delta L. The slope of the straight line relating delta t-delta L provided a measure of the velocity of shortening at zero load, V0. 3. V0 was compared with force-velocity data obtained at finite loads (load-clamp recordings). The predicted velocity of shortening at zero load, derived by hyperbolic extrapolation from velocities at low and intermediate loads, was not significantly different from V0. 4. The temperature dependence of isometric force and of shortening velocity was investigated between 2 and 12 degrees C in the same fibres. Q10 was 2.67 +/- 0.07 (S.E. of mean, n = 6) for V0 and 1.24 +/- 0.01 for tetanic force. 5. The velocity of unloaded shortening was determined at different sarcomere lengths in the range 1.4--3.1 microns. V0 was constant between 1.65 microns and approximately 2.7 microns. It decreased below 1.65 microns and increased above 2.7 microns. 6. The decrease in velocity at short sarcomere lengths probably reflects an increase of the passive resistance to shortening. The increase in velocity at long sarcomere lengths can be accounted for by the passive compressive force that is produced by the parallel elastic elements of the prestretched fibre. 7. V0 was determined at the peak of the twitch and during the plateau of the fused tetanus in the same fibre. Whereas the peak twitch force varied between 38 and 85% of the tetanic tension in the different fibres (mean: 71 +/- 5%, n = 8), V0 during the twitch was 99 +/- 2% of the value recorded during the tetanus. Depression of the isometric twitch amplitude to 10% of the control value by dantrolene did not cause any significant reduction of V0.

Animals↗
PubMed1978

Enhancement of mechanical performance by stretch during tetanic contractions of vertebrate skeletal muscle fibres.

1. Single fibres from the semitendinosus muscle of Rana temporaria were stretched during fused tetanic contractions and tension and sarcomere length (laser diffraction) responses were recorded. 2. Stretch of the fibres caused proportional increases in length of the sarcomeres. The force increased to a plateau value which was maintained during stretch or increased to a plateau value which was maintained during stretch or increased slightly. 3. The plateau value of force during stretch was dependent upon the velocity of stretch, was independent of the amplitude of stretch and was not proportional to overlap of thick and thin filaments. 4. There was enhancement of force after stretch compared with that produced at the same sarcomere length during isometric tetani. This force enhancement was independent of the velocity at which the stretch had been applied. 5. At sarcomere lengths between 1.9 and 2.3 micrometer, the force enhancement after stretch declayed rapidly, was independent of amplitude of stretch above approximately 25 nm per sarcomere not associated with a shift of the force--velocity curve. At sarcomere lengths above 2.3 micrometer the force enhancement after stretch decayed very slowly and was still present after 4 sec in long tetani. 6. At sarcomere lengths above 2.3 micrometer, force enhancement after stretch increased with amplitude of stretch and increased for any given stretch amplitude with sarcomere length. The force recorded after stretch was thus not proportional to overlap of thick and thin filaments. 7. At sarcomere lengths above 2.3 micrometer, the force enhancement after stretch was associated with a shift towards higher force value of the force--velocity curve. The velocity of shortening and zero load (V max) derived by hyperbolic extrapolation of the force--velocity curve was not affected. 8. Tension enhancement during and after stretch has a stabilizing effect in preventing dispersion of sarcomere length, particularly on the descending limb of the length--tension curve.

Animals↗
PubMed1977

Relationship between sarcomere length and active force in rabbit papillary muscle.

Isometric peak twitch force (stimulation frequency 0.5/s; 29.5-30.5 degrees C) was correlated with sarcomere length in isolated papillary muscles of the rabbit. Sarcomere length was measured from photographic recordings (1.5 ms exposure time) performed at rest between contractions and at the time of isometric peak twitch force. The sarcomere length at rest was found to be relatively uniform throughout the preparation and to be linearly related to the overall muscle length within the range Lmax-0.85Lmax. The distribution of sarcomere lengths increased considerably as the muscle went from rest to activity. Studies of surface markers showed different degrees of shortening (or elongation) of individual segments along the length of the preparation. The mean resting sarcomere length at Lmax (the optimum muscle length for force production) was 2.44 +/- 0.01 micron (grand mean +/- S.E., 7 muscles). The means active sarcomere length at Lmax was 2.29 +/- 0.04 micron. Active force declined steeply as the muscle length was reduced below Lmax. At a resting sarcomere length of 2.0 micron, active force was approximately 1/3 of the maximum. The observed differences between the length-tension relat-onships in myocardium (twitch responses) and skeletal muscle (tetanic contractions) are discussed on the basis of a length dependency of the activation process in cardiac muscle.

Animals↗
PubMed1977

The force-velocity relationship in vertebrate muscle fibres at varied tonicity of the extracellular medium.

1. The relationship between active force and velocity of shortening was studied during tetanic contraction of isolated semitendinosus muscle fibres of the frog (0.5-2.0 degrees C). Measurements were carried out with the fibre immersed in isotonic (1.00R) Ringer solution and in solutions that were made hypotonic by reduction of NaCl (osmolality 0.62 and 0.81 of normal Ringer) and hypertonic by addition of sucrose (osmolality 1.22 and 1.44 of normal Ringer).2. The force-velocity relation was hyperbolic at loads lower than 80% of measured isometric force (P(0)) but exhibited a reversed curvature between 0.8P(0) and P(0). The maximum velocity of shortening was determined in two different ways: (i) by extrapolation to zero load from force-velocity data truncated at 0.8P(0) (computer fitting of hyperbola, leastsquares method) and (ii) by recording the time required to take up the slack of the fibre after a quick release during tetanus.3. Isometric force and maximum speed of shortening both changed inversely with the tonicity of the extracellular medium. Immersion of the fibre in 0.81R hypotonic solution caused active tension and shortening velocity to increase by 10 +/- 1% (mean +/- S.E. of mean, n = 14) and 12 +/- 1%, respectively. Conversely, force and shortening velocity decreased by 12 +/- 1% (n = 13) and 22 +/- 2% when normal Ringer was replaced by 1.22R hypertonic solution. These changes doubled when the tonicity was altered from normal Ringer to 0.62R and 1.44R, respectively.4. Changes in fibre cross-sectional area equivalent to those obtained in the 0.81R and 1.22R solutions (+11% and -13%, respectively) were produced by varying the sarcomere length within the range 2.0-2.5 mum in the normal Ringer solution. Maximum velocity of shortening remained very nearly constant under these conditions, indicating that the shortening velocity, like the isometric force, is not critically dependent on changes in myofilament lattice width over the range considered.5. The results support the view that both shortening velocity and active force are modulated by changes of the intracellular ionic strength above and below the level that normally exists in the intact muscle fibre.

Animals↗
PubMed1976

Non-hyperbolic force-velocity relationship in single muscle fibres.

The force-velocity relation has been studied in sixteen single fibres from frog semitendinosus muscle with particular attention to the high-force portion of the curve. The force-velocity curve was hyperbolic except for a reversal of curvature near 80% measured isometric tension (PO). Rectangular hyperbolas fitted (linear, least-squares method) these data well only when values below 0.78 PO were considered. Extrapolation of these hyperbolas above 0.78 PO gave predicted isometric tensions (P*O) which averaged 32+/-6% above the measured PO values. Hill's constants (1.84 degrees C) for these hyperbolas were: a/P*O=0.177+/-0.021, b=0.329+/- 0.035 M.L./sec, Vmax=1.91+/-0.074 M.L./sec. The reversal of curvature persisted when force-velocity data were obtained using: 1 or 60 min response intervals, afterloaded isotonic responses, grid stimulation, electrically induced contractures and bundles of fibres. The reversal of curvature diminished when force-velocity data were obtained from slightly stretched fibres (about 2.3 mum sarcomere length as compared to 2.1 mum in the control). The results indicate that sarcomere length redistributions probably do not account for the non-hyperbolic force-velocity relation. An explanation for the behavior based on the geometry of the contractile filament lattice is discussed.

Animals↗
PubMed1976

The contractile state of rabbit papillary muscle in relation to stimulation frequency.

1. The relationship between active force and stimulation frequency (0-25-5/sec) was studied at 36-37 degrees C in isolated papillary muscles of the rabbit. 2. The muscle's force producing capability at a given frequency was determined as the isometric twitch response to a test stimulus that was applied at various times after a priming period. The optimum contractile response was obtained at an interval of 0-8 sec between the test pulse and the last stimulus of the priming period. 3. The optimum contractile response exceeded the steady-state twitch amplitude at all stimulation frequencies higher than 1/sec. While the steady-state twitch resonse declined at frequencies higher than 4/sec, the optimum contractile response was steadily increased as the stimulation frequency was raised. 4. The optimum contractile response was also determined after priming the muscle with a sinusoidal a.c. pulse (field strength, 10 V (r.m.s.)/cm; frequency, 20 c/s; duration, 2-5 sec). The optimum contractile response obtained after a.c. stimulation was 2-2 times greater than the maximal steady-state response. Its absolute value was 67-3+/-6-1 mN/mm2 (mean +/-S.E. of mean, n = 6). 5. The twitch potentiation produced by priming the muscle at a given frequency decayed exponentially in two phases after optimum contractile response had been attained. The time constants of the two phases, determined after a.c. stimulation, were 2-6+/-0-8 (n = 4) and 92-0+/-13-3 sec (n = 7), respectively. 6. The optimum contractile response determined at various stimulation frequencies was linearly related to the fraction of time during which the cell membrane was depolarized (beyond -40 mV) by the action potentials. 7. The results are interpreted in terms of a two-component model of the metabolism of activator calcium in the excitation-contraction coupling.

Action Potentials↗
PubMed1975

Mechanical deactivation induced by active shortening in isolated muscle fibres of the frog.

1. The effect of active shortening on the time course and magnitude of isometric tension development during a single twitch and during an incompletely fused tetanus was studied at 0-2-1-2 degres C in isolated semitendinosus muscle fibres of the frog. 2. Active shortening caused a depression of the contractile force without markedly affecting the total duration of the twitch. The depressant effect increased with increasing amounts of sarcomere shortening. Sarcomere shortenings of 0-05 mum and 0-3 mum reduced the twitch force by approximately 5 and 20 percent of the maximal tetanic tension, respectively. 3. A given sarcomere shortening induced the same absolute amount of depression of the contractile strength when the movement was carried out at different times during the initial 200-250 msec after the stimulus. 4. The influence of load and velocity of shortening during the movement phase was studied. Differences in load ranging between zero and 1/3 of the maximal tetanic tension (with concomitant changes in speed of shortening from Vmax to approximately 1/5 of Vmax) did not affect the degree of depression markedly. Underthe conditions studied, the extent of movement appeared to be the only significant determinant of the depressant effect. 5. The reduction in force induced by active shortening persisted for 800-900 msec during an incompletely fused tetanus. 6. It is suggested that the depressant effect is based on a structural change in the myofilament system that is produced as the A and I filaments slide along each other during muscle activity.

Animals↗