Effect of amiodarone on the dynamics of mechanical restitution of rat papillary muscles

We studied the effect of amiodarone (class III antiarrhythmic drug) on the dynamics of mechanical restitution of rat papillary muscle. Amiodarone produced a weak negative inotropic effect and stimulated potentiation of contractility of the muscle preparation after short-term (4-60 sec) cessation of its electrical stimulation. On the other hand, the time of attaining half-maximum amplitude of contractions after amiodarone treatment did not differ from the control. Analysis of curves presenting the drop of potentiation of muscle preparation contractility after resumption of regular electrical stimulation after 60-sec arrest until attaining a stable level showed that the amplitude returned to the initial level by the 9thcontraction-relaxation cycle both in the control and after amiodarone treatment. Coefficient of the drop of contraction amplitude potentiation was virtually the same in the two groups. Presumably, amiodarone does not modulate calcium-binding capacity of the sarcoplasmic reticulum, but improves Ca retention in the sarcoplasmic reticulum stores.     

Myocardial force interval relationships: influence of external sodium and calcium,muscle length,muscle diameter and stimulation frequency

Several inotropic interventions were studied in thin papillary muscles under dynamic conditions. The effects on mechanical restitution and postextrasystolic potentiation were analysed. The decay of postextrasystolic potentiation was taken as a measure of recirculation fraction of activator calcium. The mechanical restitution curve had a plateau phase on its rising phase which was abolished in low extracellular sodium hut pronounced in increased extracellular calcium. The recirculation fraction (RF) in control was 0.35±0.03; lowering the extracellular sodium by 200, increased the RF to 0.46±0.04 (n= 10). A reduction of sodium by 40%, increased the RF to 0.57±0.04, whereas increasing extracellular calcium to 4 mm gave an RF of 0.48±0.05 (n= 10 in all cases). There was no significant effect on RF of changing basic stimulation frequency or muscle preparation length. These findings support RF as a good index of myocardial contractility. Furthermore, at muscle diameters above 0.65 mm the RF was found to he reduced, suggesting this diameter as critical for muscle function. Also, postextrasystolic potentiation in relation to preceding steady state contraction was markedly increased at these diameters. In conclusion, this study shows that RF is independent of stimulation frequency and muscle length, and that it is increased when calcium extrusion by the sodium/calcium exchange is reduced. Furthermore, RF is critically dependent upon the diameter of the preparation and mechanical restitution is changed by altered extracellular sodium concentration.     

Myocardial force interval relationships: influence of external sodium and calcium, muscle length, muscle diameter and stimulation frequency.

Several inotropic interventions were studied in thin papillary muscles under dynamic conditions. The effects on mechanical restitution and postextrasystolic potentiation were analysed. The decay of postextrasystolic potentiation was taken as a measure of recirculation fraction of activator calcium. The mechanical restitution curve had a plateau phase on its rising phase which was abolished in low extracellular sodium but pronounced in increased extracellular calcium. The recirculation fraction (RF) in control was 0.35 +/- 0.03; lowering the extracellular sodium by 20% increased the RF to 0.46 +/- 0.04 (n = 10). A reduction of sodium by 40% increased the RF to 0.57 +/- 0.04, whereas increasing extracellular calcium to 4 mM gave an RF of 0.48 +/- 0.05 (n = 10 in all cases). There was no significant effect on RF of changing basic stimulation frequency or muscle preparation length. These findings support RF as a good index of myocardial contractility. Furthermore, at muscle diameters above 0.65 mm the RF was found to be reduced, suggesting this diameter as critical for muscle function. Also, postextrasystolic potentiation in relation to preceding steady state contraction was markedly increased at these diameters. In conclusion, this study shows that RF is independent of stimulation frequency and muscle length, and that it is increased when calcium extrusion by the sodium/calcium exchange is reduced. Furthermore, RF is critically dependent upon the diameter of the preparation and mechanical restitution is changed by altered extracellular sodium concentration.     

M-wave modulation at relative levels of maximal voluntary contraction

Frequency (mean and median power frequency, f and f _m) and amplitude (average rectified and root mean square values, ARV and rms), parameters of the M-wave, and the dorsiflexor force parameters of the anterior tibial muscles were measured in seven healthy human subjects. Intermittent, voluntary contractions at relative intensities (40%, 60%, and 80%) of maximal voluntary contraction (MVC) were performed in conjunction with electrical stimulation. The M-wave parameter changes were measured over the course of the isometric contractions. At higher force levels, M-wave potentiation was observed as increases in both ARV and rms. The ARV augmentation attained levels as high as 206.1 (SD 7.4)% of resting values after both initial and final contractions of 80% MVC, reaching statistical significance (P < 0.01). The f and f _m failed to show a significant difference at any level of contraction. It was surmised that potentiation of the M-wave was the result of an increased contribution of muscle fibre type IIb recruited during higher contraction levels, reflecting the change to larger, deeper innervating motoneurons as the intensity of contraction, as a percentage of MVC, rose. Recruitment of type IIb fibres, which have been reported to have a higher energy potential and frequency content, were thought to reflect changes in the local, excitability threshold of some motor units as the force intensity increased during the intermittent voluntary contractions. It is suggested that the M-wave elicited after contractions has the potential to reflect, to some extent, motor unit recruitment changes resulting from the preceding contractions, and that through comparisons of M-wave amplitude parameters, contributions of varying fibre types over the course of a contraction may be indicated.     

Inotropic mechanisms of amrinone in papillary muscles from guinea-pig hearts

Isometric force and action potentials were recorded in papillary muscles from guinea-pigs (temperature 33 degrees C, stimulation frequency 0.5 Hz). Amrinone (1 mM) increased peak twitch force (to 220% of control, n = 12) and rate of rise of force (to 221% of control, n = 12), while time from peak to half-relaxation was markedly reduced (to 70% of control). The time to peak force was not significantly changed. Action potential at 50% repolarization was shortened (93.3% of control, n = 8), whereas plateau voltage became more positive. Peak twitch force in response to a test stimulus after a varied interval, i.e. mechanical restitution, was increased at all intervals by the drug. However, the time to full mechanical restitution (1.5 s) was not affected. Forces in response to the test interval preceding the previous contraction (post-extrasystolic potentiation) were analysed. Maximum potentiation was 16.0 mN mm-2 (2.7 +/- 0.4%) before and 22.6 mN mm-2 (1.7 +/- 0.1%) after addition of the drug, i.e., the relative potentiation was diminished in the presence of the drug. The test interval for optimum potentiation was shortened from 370 to 320 ms (P less than 0.05, n = 12) in 1 mM amrinone. During decay of post-extrasystolic potentiation peak force of the post-potentiated contraction was linearly related to force of the potentiated contraction. The slope of this line (which is believed to monitor recirculation of activator calcium) was increased by amrinone from 0.37 to 0.50 (P less than 0.01, n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)     

Short-term effects of stimulus interval changes in guinea-pig and rat atrial muscle

Isometric force and action potentials were recorded in thin atrial strips from guinea-pigs and rats (32 degrees C). The restitution of peak force and action potential duration, after a regular contraction, was determined (test interval 0.1-120 s), together with the post-extrasystolic potentiation. The mechanical restitution could be described with an exponential function in two phases as: force = A(I-e-k1t) + B(I-e-k2t). By increasing the basic stimulation rate in guinea-pig atria from 0.2 to 2 Hz, the size of A was approximately doubled while B was only slightly affected. When [Ca2+] was increased from 0.9 to 3.6 mmol l-1, the size of A increased approximately 3.4 times while B decreased only slightly. There was a close correlation between steady-state contractility of the muscle and parameter A but not parameter B. In a similar fashion post-extrasystolic potentiation can be described as: force = Ce-kt + D. This potentiation was greater in guinea-pig than in rat hearts. In both species the rate of potentiation decay (k) was usually similar to the rate of the first phase of restitution (k1). It seems reasonable to interpret the parameters A and B as reflections of two separate intracellular compartments for activator calcium.     

Analysis of mechanical alternans in rabbit papillary muscle

Isometric force and action potentials were recorded in rabbit papillary muscles. It was found that the monophasic decline of the contractile potentiation that was recorded after an extrasystole (ES) was replaced by transient mechanical alternans (TMA) when temperature and calcium concentration of the perfusion medium had been lowered (from 37 degrees to 27 degrees C and from 2.0 to 0.5 mM, respectively). TMA in response to ES was also seen when the preparation was exposed to 2mM 4-aminopyridine. Furthermore, TMA could be induced by a shortening step during activity. Mechanical restitution curves were recorded by relating max. rate of force development of a test contraction to the duration of the preceding stimulus interval. It was found that the alternating contractions during TMA were associated with shifts of the mechanical restitution curve along the force axis. The duration of the action potential was inversely related to force development during TMA. It is proposed that TMA is due to a reduced damping of a regulatory feedback system between inotropic state and intake of activator calcium during the action potential. The following sequence of events are suggested: The abbreviated action potential accompanying a potentiated contraction is associated with reduced intake of activator calcium. This leads to depression of the subsequent contraction. The latter contraction is associated with increased calcium intake due to prolongation of the action potential. This will lead to potentiation of the next beat and the sequence is repeated. It is proposed that recirculation of calcium between heart beats will act as a damping factor of this system.     

The action of 2,3-butanedionemonoxime on the inotropic state in guinea-pig myocardium

Isolated papillary muscles from guinea-pig right ventricles were used (temperature 33 °C, stimulation frequency 0.5 Hz). Isometric twitch and action potentials were recorded. Upon addition of 2, 3-butanedionemonoxime (BDM) (2 mm) the peak twitch force was reduced from 4.17 ± 0.4 mN/mm² to 1.68 ± 0.3 mN/mm² (n = 9, P < 0.001). The time course of the isometric twitch was slightly altered. Time to peak tension (TPT) was reduced by 12.0 ± 3% (n = 9, P < 0.001) whereas time to half relaxation (THR) was left unaffected. The rate of rise offorce was reduced by 35 ± 3.2 mN/mm²s i.e. 46 ± 3 %. The action potential duration and amplitude was not significantly changed by the drug. The shape of the curve relating peak twitch force of an extra beat to the preceding test interval, i.e. mechanical restitution, was affected by 2 mM 2,3-butanedionemonoxime. The curve reached its maximum faster after addition of the drug. Maximum postextrasystolic potentiation (force in response to the prepreceding test interval) was 3.2 ± 0.4 mN/mm² in 2 mm 2,3-butanedionemonoxime and 7.6 ± 0.7 mN/mm² in control (n= 6). However the percentage potentiation was very similar in control (82%) and in presence of 2,3-butanedionemonoxime (91%). Peak twitch force in relation to peak force of the preceding potentiated contraction during decay of postextrasystolic potentiation was analysed. There was a linear relation between the variables, the slope being 0.34 ± 0.04 in control and 0.30 ± 0.02 in 2_J-butane dionemonoxime. This suggests that the drug is without an action on the fraction of calcium recirculating within the cell. As previously suggested the negative inotropic action of BDM can be explained by an action on cross-bridge kinetics, however the effects on the mechanical restitution curve suggests an additional action on the calcium handling by the sarcoplasmic reticulum.     

Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff-perfused rabbit hearts

We hypothesize that remodelling of action potential and intracellular calcium (Ca_i) dynamics in the peri-infarct zone contributes to ventricular arrhythmogenesis in the postmyocardial infarction setting. To test this hypothesis, we performed simultaneous optical mapping of Ca_i and membrane potential ( V _m) in the left ventricle in 15 rabbit hearts with myocardial infarction for 1 week. Ventricular premature beats frequently originated from the peri-infarct zone, and 37% showed elevation of Ca_i prior to V _m depolarization, suggesting reverse excitation–contraction coupling as their aetiology. During electrically induced ventricular fibrillation, the highest dominant frequency was in the peri-infarct zone in 61 of 70 episodes. The site of highest dominant frequency had steeper action potential duration restitution and was more susceptible to pacing-induced Ca_i alternans than sites remote from infarct. Wavebreaks during ventricular fibrillation tended to occur at sites of persistently elevated Ca_i. Infusion of propranolol flattened action potential duration restitution, reduced wavebreaks and converted ventricular fibrillation to ventricular tachycardia. We conclude that in the subacute phase of myocardial infarction, the peri-infarct zone exhibits regions with steep action potential duration restitution slope and unstable Ca_i dynamics. These changes may promote ventricular extrasystoles and increase the incidence of wavebreaks during ventricular fibrillation. Whereas increased tissue heterogeneity after subacute myocardial infarction creates a highly arrhythmogenic substrate, dynamic action potential and Ca_i cycling remodelling also contribute to the initiation and maintenance of ventricular fibrillation in this setting.     

Posttetanic potentiation of primary response and late negative wave in the somatosensory region of the cortex of the cat

The experiments were carried out on cats under nembutal anesthesia. Stimulation of the ventroposterolateral nucleus of the thalamus or the white matter by a single stimulus elicited a primary response in the middle layers of the somatosensory cortex, and after it, a late negative wave, the duration of which reaches 40–70 msec. This potential does not have dipole reflection on the surface of the cortex and is apparently generated primarily by stellate cells. As a result of the tetanization of the ventroposterolateral nucleus or the white matter, a sharp increase in the amplitude of the late negative wave is observed, i. e., its postteanic potentiation, while the primary response changes to a significantly lesser degree. Posttetanic potentiation is observed for 2–2.5 h. Posttetanic potentiation of the late negative wave is probably governed by processes occurring at the level of the middle layers of the cerbral cortex.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 75, No. 10, pp. 1328–1334, October, 1989.     

Potentiation of isometric and isotonic contractions during high-frequency stimulation

Activity dependent potentiation is an enhanced contractile response resulting from previous contractile activity. It has been proposed that even a maximal effort contraction may be enhanced by prior activity if there is an increase in the peak rate of force development. This should increase the peak active force during a very brief maximal effort contraction. The purpose of these experiments was to evaluate potentiation during brief sequential contractions with high-frequency stimulation. For this experiment, the rat medial gastrocnemius muscle was isolated in situ. Sequential stimulation (two contractions per second for 4 s) with 200, 300, or 400 Hz doublets, triplets, and quadruplets was applied. A small degree of force potentiation was observed in isometric contractions at the reference length (RL), but the activity dependent potentiation of isometric contractions was greater at short muscle length. For example, peak rate of force development for 200 Hz doublets increased significantly from the first to the eighth contraction (from 0.30 ± 0.02 to 0.34 ± 0.02 N·s⁻¹ at RL and from 0.18 ± 0.02 to 0.28 ± 0.01 N·s⁻¹ at RL-3 mm). During isotonic contractions, there were significant increases in peak shortening from the first to the eighth contraction. With 200 Hz doublet stimulation, shortening increased from 0.85 ± 0.14 to 1.14 ± 0.17 mm, and this corresponded with an increase in peak velocity (from 116 ± 18 to 136 ± 19 mm·s⁻¹). Remarkably, even 400 Hz quadruplets showed a significant increase in shortening during repeated contractions (2 s⁻¹). These observations indicate the possibility that activity dependent potentiation can result in significant improvement in both isometric and dynamic contractions, even when activated at very high frequency.     

The contractile and electrophysiological effects of rolipram in guinea-pig papillary muscles and isolated ventricular myocytes

Isometric force, action potentials and in voltage-clamp 1st (second inward current) and its current voltage relation were recorded in papillary muscles from guinea-pigs and from guinea-pig isolated ventricular myocytes (35–37 ^oC, 0.5-1 Hz). Rolipram (1–100 µM) had no significant effect on peak isometric twitch. The rate of rise of force and time to peak tension (TPT) was likewise unaffected. Time to half relaxation (THR) was increased in a dose-dependent manner and at 30 µM THR was prolonged by 25.3 ± 6% (n= 10, P < 0.001). The effect of 30µM rolipram on isometric force was frequency dependent. At 0.25 Hz peak force was increased by 6.3 ± 3.1% (n= 7, P < 0.05). At 2 Hz rolipram exhibited a negative inotropic effect of 9.8 ± 3.3% (n= 5, P < 0.02). Action potential duration at 90% repolarization was prolonged by 13 ± 6 ms (n= 7, P < 0.05), and there was usually no effect on resting potential or action potential amplitude. Sometimes, however, a depressed plateau was recorded. Rolipram was without effect on I¹_st and its current-voltage relations. Time to full mechanical restitution after a test interval was not changed but the shape of the restitution curve was altered. The restitution process was much slower in the presence of rolipram. Hence, peak force was lower at test intervals shorter than 800 ms. Likewise, the shape of the curve relating postextrasystolic potentiation to test interval was altered by rolipram. The interval required for maximum potentiation was increased by rolipram and did not significantly affect the recirculation fraction of activator calcium.     

Changes in contractile activity of the rabbit myocardium as a result of burn shock of varied duration

Experiments were carried out on papillary muscles isolated from the rabbit heart 10, 60, or 180 min after thermal injury to the animal. Isometric contractions were recorded during stimulation of the preparation at changing frequencies (within the range from 0.1 to 2 Hz) and during poststimulation potentiation. The degree of disturbance of myocardial contractility as a result of burns was found to increase with an increase in the duration of burn shock: In all the papillary muscles isolated 3 h after burning and in 50% of those isolated 1 h after burning the biphasic frequency-strength (f-P) relationship characteristic of the normal myocardium was converted into monophasic (the amplitude of the contractions decreased progressively with an increase in frequency) and poststimulation potentiation, normally absent, appeared. After shock lasting 10 min, poststimulation potentiation was observed only in some preparations and no change in f-P was present. The normal inotropic relationships of the myocardial rhythm were restored after a twofold increase in [Ca⁺⁺]₀ or after prolonged (3–4 h) perfusion of the preparation with normal Tyrode solution. Changes in inotropic relationships of the myocardial rhythm in burn shock were similar to the changes in f-P observed after blockade of the calcium channels with compound D-600.Laboratory of Physiology and Laboratory of Biophysical Research, A. V. Vishnevskii Institute of Surgery, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Sciences of the USSR V. N. Chernigovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 5, pp. 402–405, May, 1979.     

Twitch potentiation after voluntary versus electrically induced isometric contractions in human knee extensor muscles

Twitch potentiation in knee extensor (KE) muscles after a 7-s conditioning isometric maximal voluntary contraction (MVC trial), submaximal (25% MVC) voluntary contraction (SVC trial) and submaximal tetanic contraction (25% MVC) induced by percutaneous electrical stimulation at 100 Hz (PES trial) was compared in 12 men aged 19–25 years. Isometric twitch characteristics of KE muscles were measured before conditioning contraction and following 10-min recovery by supramaximal electrical stimulation of the femoral nerve. During MVC trial, twitch peak torque (Pt) potentiated (P < 0.05) immediately after the conditioning contraction with sharp decline during the first and third minute of recovery. No significant potentiation of twitch Pt was observed in SVC trial. During PES trial, twitch Pt was potentiated (P < 0.05) within 3–10 min of recovery. The time-course of isometric twitch was not significantly altered by conditioning contractions. It was concluded that twitch potentiation in the KE muscles differed markedly following the three conditioning contractions.     

Twitch contraction properties of plantar flexor muscles in pre- and post-pubertal boys and men

This study compared electrically evoked twitch contraction characteristics of the plantar flexor muscles in pre-pubertal (11-year-old) and post-pubertal (16-year old) boys, and young (19- to 23-year-old) men. The posterior tibial nerve was stimulated by supramaximal square-wave pulses of 1 ms duration at rest and after brief (5 s) isometric maximal voluntary contraction (MVC) of the plantar flexor muscles, i.e. during post-activation potentiation. Men had higher MVC force than boys and post-pubertal boys higher than pre-pubertal boys. Pre-pubertal boys had lower peak twitch forces (P _t) at rest and when potentiated compared with post-pubertal boys and men, whereas no significant differences were found between post-pubertal boys and men. Pre-pubertal boys had higher ratios of P _t at rest and potentiated P _t to MVC force than post-pubertal boys and men. No age-related differences were obtained in post-activation potentiation, rest and potentiated twitch contraction and half-relaxation time, and MVC force relative to body mass. The main findings of the study were that puberty is characterized by increased muscle force-generating capacity with no change in twitch potentiation and time-course characteristics, and that twitch force-generating capacity develops in an adult-like pattern after puberty. Accepted: 10 April 2000     

Changes in conduction velocity,median frequency,and root mean square-amplitude of the electromyogram during 25% maximal voluntary contraction of the triceps brachii muscle,to limit of endurance

Summary The objective of the present study was to investigate whether isometric contraction of the right triceps brachii muscle, of maximal duration and at 25% of the maximal voluntary contraction (MVC), would reduce mean fibre conduction velocity (CV) for the active motor units (MU). In addition to the cross-correlation of surface electromyograms (EMG) for CV determination, median frequency (f _m) and root-mean-square amplitude (rms-amplitude) were calculated. The initial 5 min of the recovery of the three parameters was also investigated. The MVC were performed before and after the sustained contraction. Seven males — six in their twenties and one aged 43 - participated in the investigation. Mean CV for the unfatigued muscle was 4.5 m·s^–1, SD 0.38. On average, CV decreased less than 10% during the sustained contraction (P<0.05). Thef _m decreased almost linearly (46%) during the endurance time, while three quarters of the 250% increase in rms-amplitude took place during the last 50% of the contraction (P<0.001, both parameters). The MVC was reduced by 39% immediately after exhaustion (P<0.05). During the 1st min of recovery the rms-amplitude decreased by 50%, and the fm increased from 54% to 82% of the initial value (bothP<0.05. No measurable simultaneous CV restitution occurred. A parallel 15% increase inf _m and CV took place during the last 4 min of recovery (bothP<0.001), while the amplitude remained constant. Since mean CV was essentially unchanged during the last 50% of the endurance time where large changes inf _m and rms-amplitude occurred, factors supplementary to CV probably caused the striking changes in fatigue EMG, notably —MU recruitment, synchronization of MU activity, and lowering of MU firing frequencies. Nevertheless, during the last 4 min of recovery the entire increase inf _m could be accounted for by the simultaneous increase in CV.     

Ca2+]i following extrasystoles in guinea-pig trabeculae microinjected with fluo-3 - a comparison with frog skeletal muscle fibres

Force production of cardiac muscle is highly dependent on the interval between the excitations. The aim was to investigate relations between intracellular calcium ([Ca2+]i) and force when a stimulus protocol, with three extrasystoles (ESs) at various intervals, was used. The relation between [Ca2+]i and force was compared with that in frog skeletal muscle fibre. Fluo-3 was microinjected into thin cardiac trabeculae to monitor [Ca2+]i. During steady-state [Ca2+]i consisted of a rapid rise (phase 1) that lasted until peak dF/dt (rate of force development) and was followed by a slower rise (phase 2) that coincided with the action potential and had a peak after peak force. The decline in [Ca2+]i outlasted the duration of the contraction. As the ES intervals were prolonged, there was a gradual restitution of force and of the amplitude and rate of rise of phase 1 [Ca2+]i. Peak dF/dt was linearly related to the amplitude of phase 1 [Ca2+]i during restitution and potentiation of force. Skeletal muscle fibres were loaded with fluo-3-AM. From [Ca2+]i the amount of calcium bound to troponin ([Ca-T]) as a function of time was estimated. Force production of the skeletal muscle fibre could be predicted from [Ca-T] when the signal was delayed (time constant 36 ms). This finding indicates that the recorded [Ca2+]i in skeletal muscle represents activator calcium. In cardiac muscle probably only phase 1 [Ca2+]i represents activator calcium. Phase 2 [Ca2+]i probably represents calcium entry during the action potential and does not activate the contractile system to any significant extent.     

Effect of haemodynamic pressure overload of the adult ferret right ventricle on inotropic responsiveness to external calcium and rest periods

The inotropic effects of external calcium concentration ([Ca²⁺]_o] and rest periods have been compared in papillary muscles isolated from control (n=4) and pressure-overloaded right (n=5) ventricles of adult ferrets. Hypertrophy was induced by pulmonary artery clipping for 30–45 days. Under control conditions (3 mM [Ca²⁺]_o, 0.1 Hz), the isometric twitch force of hypertrophied muscles was decreased by 75%, time to peak was increased by 30% and time to half-relaxation was increased by 50% compared with non-hypertrophied preparations. The sensitivity of contraction to [Ca²⁺]_o was decreased in hypertrophied muscles compared with control ([Ca²⁺] required for half-maximal contraction: 4.1 mM vs 1.7 mM) and the maximal contraction reached at high [Ca²⁺]_o was smaller in pressure-overloaded muscles compared with control (8.3±2.0 mN mm^–2 vs 19.0±2.1 mN mm^–2 respectively). In both groups, rest periods longer than the steady-state interval were initially accompanied by a potentiation of the first post-rest contraction compared with steady-state. Peak potentiation occurred after a rest of 120 s in hypertrophied muscles and after a rest of 60 s in control. The maximal relative potentiation, i.e. compared with the steady-state twitch, was higher in hypertrophied muscles (+ 75%) than in control (+ 20%). After peak potentiation, the amplitude of the first post-rest contraction progressively decreased with increasing periods of rest, although at a slower rate in hypertrophy compared with control. The time constants of post-rest decay were 1203±99 s and 528±24 s respectively. These results suggest that intracellular Ca²⁺ availability is decreased in this model of pressure overload and cannot be compensated by an increase of [Ca²⁺]_o. The slower time course of the twitch and the decreased inotropic responsiveness to [Ca²⁺]_o in hypertrophy suggests that Ca²⁺ uptake by the sarcoplasmic reticulum (SR) is slower. A model that accounts for the time course of post-rest contractility indicates that, during rest, the rate of recovery of the Ca²⁺ release process, as well as the rate of Ca²⁺ loss from the SR, may be slower in hypertrophied preparations. The latter may possibly be due to a lower SR Ca²⁺ content and a depressed Ca²⁺ efflux through the sarcolemmal sodium/calcium exchanger.     

Locus coeruleus bursts induced by glutamate trigger delayed perforant path spike amplitude potentiation in the dentate gyrus

Summary Glutamate pressure ejections in the vicinity of locus coeruleus (LC) neurons have been shown to produce both short and long-lasting potentiation of perforant path (PP) evoked population spike amplitude in the dentate gyrus (DG). These effects of LC-glutamate activation resemble those produced by direct application of NE in vitro or in vivo. The present study monitored the cellular response of LC neurons to local glutamate ejections concomitant with stimulation of the PP evoked potential. Double barrel micropipettes or 33 ga cannulaelectrode assemblies permitted LC unit recording and glutamate ejection at or near the same site in urethane anesthetized rats. Glutamate ejections produced a burst of LC activity lasting 250–400 ms and followed by a depression of unit activity lasting 4.6 min. The maximal spike potentiation produced by LC activation was 158%. The first spike to exceed the control range occurred 34 s after the LC burst. Comparable silent intervals in LC unit activity induced by systemic clonidine were not accompanied by population spike amplitude potentiation. The mean duration of potentiation was 4.4 min except in four cases where responses remained potentiated for the duration of the experiment. The duration of potentiation was not correlated with the termination of LC depression. LC units recovered to baseline rates following glutamate induced depression of activity. The occurrence of potentiation appeared to require that glutamate activation reach a critical number of LC neurons since small glutamate ejections could produce a local burst without eliciting potentiation. Long-lasting changes were also related to larger glutamate volumes (100 nl). EPSP slope increases were briefer and occurred less frequently than spike amplitude changes suggesting EPSP-spike dissociation. The delay between the burst of LC activity and amplitude increases in the DG supports a model of NE action in which there are both rapid and slowly developing effects of NE release in the DG. In summary, brief, but intense, activation of LC neurons produces a delayed potentiation of DG responses lasting minutes to hours following the LC burst.     

Motor unit recruitment and rate coding in response to fatiguing shoulder abductions and subsequent recovery

The purpose of the present study was to investigate motor unit (MU) recruitment and firing rate, and the MU action potential (MUAP) characteristics of the human supraspinatus muscle during prolonged static contraction and subsequent recovery. Eight female subjects sustained a 30° shoulder abduction, requiring 11–12% of maximal voluntary contraction (MVC), for 30 min. At 10 and 30 min into the recovery period, the shoulder abduction was repeated for 1 min. The rating of perceived exertion for the shoulder region increased to “close to exhaustion” during the prolonged contraction, and the surface electromyography (EMG) recorded from the deltoid and trapezius muscles showed signs of local muscle fatigue. From the supraspinatus muscle, a total of 23,830 MU firings from 265 MUs were identified using needle electrodes. Of the identified MUs, 95% were continuously active during the 8-s recordings, indicating a low degree of MU rotation. The mean (range) MU firing rate was 11.2 (5.7–14.5) Hz, indicating the relative force contribution of individual MUs to be larger than the overall mean shoulder muscle load. The average MU firing rate remained stable throughout the prolonged abduction, although firing rate variability increased in response to fatigue. The average concentric MUAP amplitude increased by 38% from the beginning (0–6 min) to the end (24–29 min) of the contraction period, indicating recruitment of larger MUs in response to fatigue. In contrast, after 10 min of recovery the average MU amplitude was smaller than seen initially in the prolonged contraction, but not different after 30 min, while the MU firing rate was higher during both tests. In conclusion, MU recruitment plays a significant role during fatigue, whereas rate coding has a major priority during recovery. Furthermore, a low degree of MU rotation in combination with a high relative load at the MU level may imply a risk of overloading certain MUs during prolonged contractions. Accepted: 6 June 2000