Long-lasting inhibition of the soleus muscle H reflex related to realization of voluntary arm movements in humans

In healthy humans, we recorded the H reflex induced by transcutaneous stimulation of the tibial nerve (recording from the soleus muscle). In subjects in the lying position, we studied changes in the H reflex values after preceding voluntary arm movements realized with a maximum velocity after presentation of an acoustic signal. On the 200th to 300th msec after forearm flexion, long-lasting inhibition of the H reflex developed following a period of initial facilitation and reached the maximum, on average, 700 msec from the moment of the movement. Flexion of the contralateral upper limb in the elbow joint induced deeper inhibition than analogous movement of the ipsilateral arm. Long-lasting clear inhibition of the H reflex developed after arm flexion in the elbow joint but was slightly expressed after finger clenching. After inhibition reached the maximum, its time course was satisfactorily approximated by a logarithmic function of the time interval between the beginning of the conditioning voluntary movement and presentation of the test stimulus. Durations of inhibition calculated using a regression equation were equal to 6.6 sec and 8.5 sec after ipsilateral and contralateral elbow-joint flexions, respectively. Inhibition was not eliminated under conditions of tonic excitation of motoneurons of the tested muscle upon voluntary foot flexion. Long-lasting inhibition of the H reflex was also observed after electrical stimulation-induced flexions of the upper limb. The obtained data indicate that movements of the upper limb cause reflex long-lasting presynaptic inhibition of the soleus-muscle H reflex that can play a noticeable role in redistribution of the muscle tone during motor activity. Neirofiziologiya/Neurophysiology, Vol. 40, No. 3, pp. 221–227, May–June, 2008.     

Fatigue-induced modulation of the H reflex of soleus muscle in humans

We studied the effect of fatigue of the mm. gastrocnemius-soleus on the H reflex elicited by transcutaneous stimulation of n. tibialis and recorded from the m. soleus; healthy 18-to 34-year-old volunteers were tested. Fatigue was evoked by long-lasting (6 to 9 min) voluntary tonic static sole flexion of the foot (ankle extension) with a force equal to 75% of the maximum voluntary contraction (MVC). The amplitude of H reflex significantly (P < 0.001) decreased to about 60% of the initial value immediately after the period of fatiguing effort. Within 2 to 3 min, it relatively rapidly recovered and reached about 90% of the control, and this was followed by a period of slow recovery to about 96–97% of the initial value 30 min after conditioning fatigue. We suppose that the initial period of suppression of the H reflex results to a considerable extent in an increase in the intensity of presynaptic inhibition of transmission from Ia afferents due to tonic activation of high-threshold (groups III and IV) afferent fibers induced by intensive fatigue-related metabolic changes in the muscles. More long-lasting (tens of minutes) changes are related to slow reverse development of direct effects of fatigue-induced biochemical shifts in the muscle. Neirofiziologiya/Neurophysiology, Vol. 38, Nos. 5/6, pp. 426–431, September–December, 2006.     

State of monosynaptic reflex (H reflex) arc during voluntary muscle contraction in humans

Effect of an isometric voluntary contraction of the soleus muscle (5–6 sec in duration) on the H reflex was studied in persons aged 25–45 years. A sharp enhancement of the H reflex at a dynamic phase of fast contraction (in the force increase period) and its less pronounced increase at a static phase of contraction were shown. When a paired stimulation of the nerve was used (interstimulus interval, 500 msec), a voluntary contraction of the muscle fully abolished the first stimulus-related suppression of the second H reflex. When the muscle contracted against the background of vibration, the suppressed H reflex recovered up the the level observed in the resting muscle, but did not reach the level characteristic for the contracting muscle. The findings show that the two pathways controlling the H reflex (descending and afferent) function independently, and apparently there exist at least two corresponding groups of interneurons causing a presynaptic inhibition of the H reflex.Neirofiziologiya/Neurophysiology, Vol. 25, No. 5, pp. 365–371, September–October, 1993.     

Muscle spindle feedback differs between the soleus and gastrocnemius in humans

The Hoffmann (H) reflex and motor (M) response were studied in soleus and gastrocnemius during voluntary contraction in eight male volunteers. Aims: To determine if the strength of spindle input to the muscles is the same. To assess if the M response size changes during contraction. Results: The size of the maximum M response (M max) changed during contraction in each subject. Hence, all H reflex measurements were normalized to the M max at each level of contraction for each subject. The largest H/M max was bigger in soleus than gastrocnemius at every contraction level. The overall largest H/M max for soleus (97%) and gastrocnemius (55%) were achieved at 40 and 100% maximum voluntary contraction (MVC), respectively. Conclusion: Soleus receives greater spindle feedback than the gastrocnemius both at rest and during voluntary contraction.     

Electromechanical delay in isometric muscle contractions evoked by voluntary, reflex and electrical stimulation

Electromechanical delay (EMD) in isometric contractions of knee extensors evoked by voluntary, tendon reflex (TR) and electrical stimulation (ES) was investigated in 21 healthy young subjects. The subject performed voluntary knee extensions with maximum effort (maximal voluntary contraction, MVC), and at 30%, 60% and 80% MVC. Patellar tendon reflexes were evoked with the reflex hammer being dropped from 60°, 75° and 90° positions. In the percutaneous ES evoked contractions, single switches were triggered with pulses of duration 1.0 ms and of intensities 90, 120 and 150 V. Electromyograms of the vastus lateralis and rectus femoris muscles were recorded using surface electrodes. The isometric knee extension force was recorded using a load cell force transducer connected to the subject's lower leg. The major finding of this study was that EMD of the involuntary contractions [e.g. mean 22.1 (SEM 1.32) ms in TR 90°; mean 17.2 (SEM 0.62) ms in ES 150 V] was significantly shorter than that of the voluntary contractions [e.g. mean 38.7 (SEM 1.18) ms in MVC,P < 0.05]. The relationships between EMD, muscle contractile properties and muscle fibre conduction velocity were also investigated. Further study is needed to explain fully the EMD differences found between the voluntary and involuntary contractions.     

Long-lasting H-reflex inhibition evoked by stimulation of a nerve to the antagonist muscles and vibrational stimulation of the muscle receptors in humans

In testing of healthy subjects, we studied the influence of conditioning stimulation of then.peroneus communis on the H-reflex EMG discharge recorded from them. soleus. Two waves of inhibition separated by a period of relative facilitation of the reflex were observed. The first wave,D ₁, was not longer than 50 msec. The intensity of later inhibition (D ₂ wave) within a 500 to 4000 msec time segment linearly depended on the logarithm of the interval between the conditioning and test stimuli. Extrapolation showed that the duration of this wave could be evaluated as equal to 6.3 msec, on average. We also studied the temporal course of H-reflex inhibition after conditioning vibrational stimulation of the receptors of them. tibialis ant. andm. biceps femori. Within a 500 to 4000 msec test interval, it could also be fitted with a logarithmic dependence similar to that observed after electrical stimulation of then. peroneus comm. The duration of inhibition after vibrational stimulation of them. tibialis ant. andm. biceps femori was 6.2 and 8.9 sec, respectively. Inhibition evoked by both conditioning influences was not removed after a voluntary plantar flexion of the foot. Our observations support the statement that in humans stimulation of the afferent fibers from the antagonist muscles, as well of the muscle receptors, evokes in two-neuron reflex arcs presynaptic inhibition, whose duration reaches several seconds; this phenomenon can play a significant role in the control of muscle tone in the course of muscle performance.     

Aging effects on posture-related modulation of stretch reflex excitability in the ankle muscles in humans

The purpose of this study was to examine the effects of aging on posture-related changes of the stretch reflex excitability in the ankle extensor, soleus (SOL), and flexor, tibialis anterior (TA) muscles. Fourteen neurologically normal elderly (mean 68 ± 6 years) and 12 young (mean 27 ± 3 years) subjects participated. Under two postural conditions, upright standing (STD) and sitting (SIT), stretch reflex electromyographic (EMG) responses in the SOL/TA muscle were elicited by imposing rapid ankle dorsi-/plantar-flexion. Under the SIT condition, subjects were asked to keep the SOL background EMG level, which is identical to that under the STD condition. In the SOL muscle, both groups showed significant enhancement of the short-latency stretch reflex (SLR) response when the posture changed from SIT to STD. In the TA muscle, the young group showed significant enhancement of the middle- (MLR) and long-latency stretch reflex (LLR) when the posture changed from SIT to STD; no such modulation was observed in the elderly group. Since the TA stretch reflex responses under the STD condition were comparable in the young and elderly groups, the lack of posture-related modulation of the TA muscle in the elderly group might be explained by augmented stretch reflex excitability under the SIT condition. The present results suggest that the (1) SOL SLR responses are modulated both in the young and elderly subjects when the posture is changed from SIT to STD, (2) TA MLR and LLR responses are not modulated in the elderly subjects when the posture is changed from SIT to STD, while each response is same between the young and elderly in STD, and (3) the effect of aging on the posture-related stretch reflex differs in the SOL and TA muscles.     

Non-uniform mechanical activity of quadriceps muscle during fatigue by repeated maximal voluntary contraction in humans

To determine the non-uniform surface mechanical activity of human quadriceps muscle during fatiguing activity, surface mechanomyogram (MMG), or muscle sound, and surface electromyogram (EMG) were recorded from the rectus femoris (RF), vastus lateralis (VL), and vastus medialis (VM) muscles of seven subjects during unilateral isometric knee extension exercise. Time- and frequency-domain analyses of MMG and of EMG fatigued by 50 repeated maximal voluntary contractions (MVC) for 3 s, with 3-s relaxation in between, were compared among the muscles. The mean MVC force fell to 49.5 (SEM 2.0)% at the end of the repeated MVC. Integrated EMG decreased in a similar manner in each muscle head, but a marked non-uniformity was found for the decline in integrated MMG (iMMG). The fall in iMMG was most prominent for RF, followed by VM and VL. Moreover, the median frequency of MMG and the relative decrease in that of EMG in RF were significantly greater (P < 0.05) than those recorded for VL and VM. These results would suggest a divergence of mechanical activity within the quadriceps muscle during fatiguing activity by repeated MVC. Accepted: 19 January 1999     

Changes in the excitability of soleus muscle short latency stretch reflexes during human hopping after 4 weeks of hopping training

Changes in the excitability of the human triceps surae muscle short latency stretch reflexes were investigated in six male subjects before and after 4 weeks of progressive two-legged hopping training. During the measurements the subjects performed 2-Hz hopping with: preferred contact time (PCT) and short contact time. The following reflex parameters were examined before and after the training period: the soleus muscle (SOL) Hoffmann-reflex (H-reflex) at rest and during hopping, the short latency electromyogram (EMG) components of the movement induced stretch reflex (MSR) in SOL and medial gastrocnemius muscle (MG), and the EMG amplitude of the SOL and MG tendon reflexes (T-reflexes) elicited at rest. The main results can be summarized as follows: the SOL T-reflex had increased by about 28% (P < 0.05) after training while the MG T-reflex was unchanged; the SOL MSR (always evident) and the MG MSR (when observable) did not change in amplitude with training, and before training the SOL H-reflex in both hopping situations was significantly depressed to about 40% of the reference value at standing rest (P < 0.05). After training the H-reflex during PCT hopping was no longer depressed. As the value of the measured mechanical parameters (the total work rate, joint angular velocity and the ankle joint work rate) was unchanged after training in both hopping situations, the reflex changes observed could not be ascribed to changes in the movement pattern. To explain the observed changes, hypotheses of changes in the excitability of the stretch reflex caused by the training were taken into consideration and discussed. Accepted: 22 May 1998     

Interaction between the Postactivation Depression of H Reflex and Long-Lasting Inhibition,Evoked by Stimulation of a Nerve to the Antagonist Muscles,in Humans

In a study on healthy humans, we examined interaction of the inhibitory influences on the H reflex recorded from the m. soleus (the respective EMG discharge, evoked by stimulation of the n. tibialis comm.). Postactivation depression of the reflex was evoked by a preceding conditioning stimulation of the same nerve, while conditioning stimulation of a nerve to the antagonist muscles (n. peroneus comm.) evoked long-lasting inhibition of the reflex, which included two consecutive waves of depression, D ₁ and D ₂. When the intensity of conditioning stimulations slightly exceeded the threshold for the development of inhibitory effects, interaction between postactivation depression and both the D ₁ and D ₂ waves demonstrated mutual facilitation of these effects. When the intensity of conditioning stimuli was increased, facilitation was changed by occlusion. We conclude that afferent impulsation, evoked by homo- and heteronymous conditioning stimulations of the peripheral nerves, converges on common interneuronal populations providing long-lasting suppression of the H reflex, which develops due to depolarization of primary afferent Ia terminals.     

Threshold of the soleus muscle H-reflex is less sensitive to the change in excitability of the motoneuron pool during plantarflexion or dorsiflexion in humans

In the present study, we investigated whether weak (10% of maximal voluntary contraction) tonic dorsiflexion (DF) and plantarflexion (PF) affects the two conventional parameters used for evaluating the excitability of the soleus motoneuron (MN) pool, i.e. the ratio of the threshold of H-reflex to that of M-response (H_th:M_th) and the ratio of the maximal amplitude of H-reflex to that of M-response (H_max:M_max) in human subjects. The results showed that the H_max:M_max decreased during DF and increased during PF compared with that during rest, whereas no clear alteration was observed in H_th:M_th. These results are consistent with the scheme proposed by earlier workers, who have argued that neither inhibitory nor facilitatory effects of the conditioning stimulus apply to specific spinal reflex circuits occurring around the threshold of the test H-reflex. It is suggested, therefore, that the conventional use of the H_th:M_th ratio as a parameter reflecting the excitability of the MN pool should be reconsidered.     

Single amino-acid substitution in the N-terminal arm altered the tetramer stability of rat muscle lactate dehydrogenase A

Lactate dehydrogenase A (LDHA) is a well-characterized tetrameric enzyme. Its N-terminal arm, comprised of an α-helix and a β-strand, was suggested to be essential for subunit interactions. To examine the critical amino acid residues in the N-terminus involved in the subunit association, two single-point mutants, Leu3Pro (L3P) and Ile8Glu (I8E), have been constructed. We compared the stability of WT-LDHA (WT) and its variants by unfolding experiments. For WT, a dimeric but inactive intermediate was observed by size-exclusion chromatography at 0.6–0.8 mol/L GdmCl. Leu3Pro exists in an active tetrameric structure in aqueous solution as WT does, but it dissociates into dimers under lower concentration of GdmCl (0.2 mol/L). In aqueous solution, the Ile8Glu variant exists predominantly in the dimeric form with increased K_M and decreasedk _cat as compared with those of WT and L3P. However, the activity of Ile8Glu increases significantly in the presence of sodium sulfate. In conclusion, two mutants are less stable than WT in oligomer structure. Results also support the fact that some residues in the N-terminal arm, especially the Leu8 in the β-structure, contribute the important binding energies to the dimerization of dimers, which might affect the assembly of the enzyme as well as the catalytic function.     

Participation of galaninergic neurotransmission at the paraventricular hypothalamic nucleus in the suppression of baroreceptor reflex response by locus ceruleus in the rat

We evaluated the potential participation of galanin (GAL) at the paraventricular nucleus of hypothalamus (PVN) in the suppression of baroreceptor reflex (BRR) response by locus ceruleus (LC), using adult male Sprague-Dawley rats anesthetized with pentobarbital sodium. Microinjection of GAL (100 pmol) bilaterally into the PVN significantly depressed the BRR response. This suppressive effect was appreciably antagonized when GAL (100 pmol) and GAL antiserum (1:20) were coadministered into the bilateral PVN. Whereas bilateral microinjection of GAL antiserum into the PVN by itself elicited minimal effect, it nevertheless significantly attenuated the suppressive effect of either electrical or chemical activation of LC on the BRR response. Pretreatment with the same amount of normal rabbit serum (1:20), on the other hand, was ineffective. These results suggest that a galaninergic projection from the LC to PVN may participate in the suppression of BRR response by this dorsal pontine nucleus.     

Modulation of G(ialpha(2)) signaling by the axonal guidance molecule UNC5H2

The G protein, G(ialpha(2)), regulates a number of cellular functions including cell migration, proliferation, and differentiation. The transduction of signal depends on the ability of the alpha subunit to cycle between a GDP bound and an active GTP bound state capable of interacting with intracellular enzymes. Here, we now report the novel interaction of gip2 (constitutively activated G(ialpha(2))) with the cytoplasmic domain of UNC5H2. Like G(ialpha(2)), we found that UNC5H2 is widely expressed particularly in cells which migrate. UNC5H2 binds G(ialpha(2)) when it is charged with GTP. The interaction of G(ialpha(2)) and UNC5H2 liberated adenylyl cyclase from G(ialpha(2)) inhibition. Thus, by sequestering the alpha subunit, UNC5H2 is a novel inhibitor of G(ialpha(2)) thereby increasing intracellular cAMP levels. The expression of UNC5H2 in the brain and immune system suggests that this novel inhibitor of G protein signaling may have broad significance for axonal guidance and chemotaxis.     

Degradation of myofibrillar proteins by a calpain-like proteinase in the arm muscle of Octopus vulgaris

The effects of a calpain-like proteinase (CaDP) isolated from the arm muscle of Octopus vulgaris on the myofibrils and myofibrillar proteins isolated from the same tissue were examined. Our studies clearly showed that treatment of intact myofibrils with CaDP in the presence of 5 mM Ca²⁺ results in the degradation of the major myofibrillar proteins myosin, paramyosin, and actin. From the isolated α- and β-paramyosins only β-paramyosin is degraded by CaDP in the presence of 5 mM Ca²⁺ producing three groups of polypeptides of 80, 75, and 60 kDa, respectively. The degradation rate depends on the proteinase to substrate ratio, temperature, and time of proteolysis and is inhibited by the endogenous CaDP inhibitory factor (CIF), as well as by various known cysteine proteinase inhibitors (E-64, leupeptin, and antipain). From the other myofibrillar proteins examined myosin, but not actin, is degraded by CaDP; myosin heavy chain (MHC, 200 kDa) is degraded by CaDP producing four groups of polypeptides of lower molecular masses (155, 125, 115, and 102 kDa, respectively); the degradation rate depends on the incubation time and the proteinase to substrate ratio. Furthermore, CaDP undergoes limited autolysis in the presence of both the exogenous casein and the endogenous β-paramyosin producing two large active fragments of 52 and 50.6 kDa, respectively; CIF reversibly inhibits this CaDP autolysis. Accepted: 26 May 2000     

Inhibitory Modulation by Sodium Ions of the N-Methyl-D-Aspartate Recognition Site in Brain Synaptic Membranes

Specific binding of radiolabeled L-glutamic acid (Glu) was examined using rat brain synaptic membranes treated with a low concentration of Triton X-100. The binding drastically increased in proportion to increasing concentrations of the detergent used up to 0.1%. Addition of 100 mM sodium acetate significantly potentiated the binding in membranes not treated with Triton X-100, whereas it markedly inhibited the binding in Triton-treated membranes. The binding in Triton-treated membranes was inversely dependent on incubation temperature and reached a plateau within 10 min after the initiation of incubation at 2 degrees C, whereas the time required to attain equilibrium at 30 degrees C was less than 1 min. Sodium acetate invariably inhibited the binding detected at both temperatures independently of the incubation time via decreasing the affinity for the ligand. The binding was significantly displaced by agonists and antagonists for an N-methyl-D-aspartate (NMDA)-sensitive subclass of brain excitatory amino acid receptors, but not by those for the other subclasses. Inclusion of sodium acetate reduced the potencies of NMDA agonists to displace the binding without virtually affecting those of NMDA antagonists. Moreover, sodium ions inhibited the ability of Glu to potentiate the binding of N-[3H] [1-(2-thienyl)cyclohexyl]piperidine to open NMDA channels in Triton-treated membranes. These results suggest that sodium ions may play an additional modulatory role in the termination process of neurotransmission mediated by excitatory amino acids via facilitating a transformation of the NMDA recognition site from a state with high affinity for agonists to a state with low affinity.