The effects of acute and prolonged muscle vibration on the function of the muscle spindle’s reflex arc

Abstract

Purpose:?Localized mechanical vibration, applied directly to a muscle, is known to have powerful, duration-dependent effects on the muscle spindle’s reflex arc. Here, the conditioning of the function of the spindle reflex arc via vibration was examined with considerations for use as a non-invasive, sensorimotor research tool.

Methods:?Muscle spindle function was examined with patellar tendon taps prior to and following exposure to muscle vibration applied to the quadriceps femoris for acute (<5?s) and prolonged (20?min) durations. Surface electromyography (sEMG), torque, and accelerometry signals were obtained during the taps to quantify various measures of reflex magnitude and latency.

Results:?Our findings suggest that acute vibration had no effect on normalized reflex torque or sEMG amplitude (p?>?0.05), but increased total reflex latency (p?=?0.022). Alternatively, prolonged vibration reduced normalized reflex torque and sEMG amplitude (p?<?0.001), and increased reflex latency (p?<?0.001).

Conclusions:?Our findings support the use of prolonged vibration as a practical means to decrease the function of the muscle spindle’s reflex arc. Overall, this suppressive effect was evident in the majority of subjects, but the extent was variable. This approach could potentially be used to help delineate the muscle spindle’s role in various sensory or motor tasks in which more direct measures are not feasible. Acute vibration, however, did not potentiate muscle spindle function as hypothesized. Rather, our results suggest that acute vibration increased total reflex latency. Accordingly, potential mechanical and neurophysiological mechanisms are discussed.     

Is the spring quality of muscle plastic?

During locomotion, major muscle groups are often activated cyclically. This alternate stretch-shorten pattern of activity could enable muscle to function as a spring, storing and recovering elastic recoil potential energy. Because the ability to store and recover elastic recoil energy could profoundly affect the energetics of locomotion, one might expect this to be an adaptable feature of skeletal muscle. This study tests the hypothesis that chronic eccentric (Ecc) training results in a change in the spring properties of skeletal muscle. Nine female Sprague-Dawley rats underwent chronic Ecc training for 8 wk on a motorized treadmill. The spring properties of muscle were characterized by both active and passive lengthening force productions. A single "spring constant (Deltaforce/Deltalength) from the passive length-tension curves was calculated for each muscle. Results from measurements on long heads of triceps brachii muscle indicate that the trained group produced significantly more passive lengthening force (P = 0.0001) as well as more active lengthening force (P = 0.0001) at all lengths of muscle stretch. In addition, the spring constants were significantly different between the Ecc (1.71 N/mm) and the control (1.31 N/mm) groups. A stiffer spring is capable of storing more energy per unit length stretched, which is of functional importance during locomotion.     

Redundancy or heterogeneity in the electric activity of the biceps brachii muscle? Added value of PCA-processed multi-channel EMG muscle activation estimates in a parallel-fibered muscle

Conventional bipolar EMG provides imprecise muscle activation estimates due to possibly heterogeneous activity within muscles and due to improper alignment of the electrodes with the muscle fibers. Principal component analysis (PCA), applied on multi-channel monopolar EMG yielded substantial improvements in muscle activation estimates in pennate muscles. We investigated the degree of heterogeneity in muscle activity and the contribution of PCA to muscle activation estimates in biceps brachii (BB), which has a relatively simply parallel-fibered architecture. EMG-based muscle activation estimates were assessed by comparison to elbow flexion forces in isometric, two-state isotonic contractions in eleven healthy male subjects. Monopolar EMG was collected over the entire surface of the BB with about 63 electrodes. Estimation quality of different combinations of EMG channels showed that heterogeneous activation was found mainly in medio-lateral direction, whereas adding channels in the longitudinal direction added largely redundant information. Multi-channel bipolar EMG amplitude improved muscle activation estimates by 5–14% as compared to a single bipolar. PCA-processed monopolar EMG amplitude yielded a further improvement of (12–22%). Thus multi-channel EMG, processed with PCA, substantially improves the quality of muscle activation estimates compared conventional bipolar EMG in BB.     

Alterations in the expression of the β-cytoplasmic and the γ-smooth muscle actins in hypertrophied urinary bladder smooth muscle

The obstruction of the bladder outlet induces a marked increase in bladder mass, and this is accompanied by reduced contractility of bladder smooth muscle and alteration in the cellular architecture. In this study, we show that the composition of various isoforms of actin, a major component of the contractile apparatus and the cytoskeletal structure of smooth muscle, is altered in response to the obstruction-induced bladder hypertrophy. Northern blot analysis of the total RNA isolated from hypertrophied urinary bladder muscle, using a cDNA probe specific for smooth muscle -actin, shows over 200% increase in the -actin mRNA. However, the estimate of the amount of actin from the 2D gel reveals only a 16% increase in -actin, since the 2D gel electrophoresis does not distinguish -smooth muscle actin from -cytoplasmic actin. The bladder smooth muscle -actin and the smooth muscle -actin mRNA are not altered in response to the hypertrophy. The obstructed bladder also reveals a decrease in the -cytoplasmic actin (37%) and a concomitant diminution in the -cytoplasmic actin mRNA (29%). Hence, the composition of the actin isoforms in bladder smooth muscle is altered in response to the obstruction-induced hypertrophy. This alteration of the actin isoforms is observed at both the protein and mRNA levels.     

Does the velocity sensitivity of muscle spindles stabilize the stretch reflex?

A model of the stretch reflex based on detailed experimental studies of muscles, muscle receptors and reflex pathways has been analysed. Muscle receptors respond to the velocity and the acceleration of movement, as well as to muscle length. The effect of the velocity sensitivity on the stability of the stretch reflex is considered. It is concluded that the velocity sensitivity can compensate to some extent for the sluggishness of muscles and the delays introduced by reflex pathways. However, the value of velocity sensitivity found experimentally is greater than that required to stabilize the stretch reflex optimally. The velocity sensitivity will have some tendency to produce oscillation, and it is suggested that a small degree of oscillation may be beneficial to linearize muscle properties.     

Does titin regulate the length of muscle thick filaments?

The protein titin has been localized by electron microscopy of myofibrils labelled with monoclonal antibodies. The data are consistent with individual titin molecules extending from near the M-line to beyond the ends of thick filaments, a distance of approximately 1 micron. In the A-band, titin appears to be bound to thick filaments, probably to the outside of the filament shaft. Molecules of titin in this configuration provided an obvious mechanism by which the length of thick filaments could be regulated accurately.     

NANC relaxation of the circular smooth muscle of the oesophagus of the Agama lizard involves the l-arginine–nitric oxide synthase pathway

On carbachol (CCh; 10–30 μM) pre-contracted circular muscle strips of the Agama lizard oesophagus, electrical field stimulation evoked frequency-dependent relaxations in the presence of guanethidine (1 μM) and indomethacin (1 μM). These non-adrenergic inhibitory responses were concentration-dependently inhibited by the nitric oxide synthase (NOS) inhibitor N^ω-nitro-l-arginine methyl ester (l-NAME) within a concentration range of 30–300 μM but not d-NAME (up to 300 μM), although a component remained at 4–16 Hz even with 300 μM l-NAME. The inhibition by l-NAME (300 μM) was completely prevented when l-arginine (l-Arg; 15 mM) but not d-Arg (up to 15 mM) was applied simultaneously with l-NAME (300 μM). Increasing the l-NAME concentration to 1 mM had no additional inhibitory effect. Sodium nitroprusside (SNP) concentration-dependently relaxed pre-contracted oesophageal strips, l-NAME (up to 300 μM) had no effect. Neither adenosine 5′-triphosphate (up to 0.1 mM) nor vasoactive intestinal polypeptide (up to 0.1 μM) caused the pre-contracted oesophagus to relax. This study has shown that the NANC inhibitory response of the Agama lizard oesophagus circular muscle largely involves the l-Arg-NOS pathway as seen by the effect of l-NAME, l-Arg and SNP. The identity of the l-NAME-resistant component(s) and the lack of effect of tetrodotoxin (up to 3 μM) and ω-conotoxin GVIA (up to 0.1 μM) in relation to the nature of the inhibitory response are discussed.     

The role of PGC-1α in the regulation of skeletal muscle metabolism

The purpose of this review was to provide an understanding of the role of PGC-1α in the regulation of skeletal muscle metabolism and to describe the results of studies on the association of the polymorphism gene PPARGC1A with human muscle performance.     

What limits the velocity of fast-skeletal muscle contraction in mammals?

In rat skeletal muscle the unloaded shortening velocity (Vo) is defined by the myosin isoform expressed in the muscle fibre. In 2001 we suggested that ADP release from actomyosin in solution (controlled by k(-AD)) was of the right size to limit Vo. However, to compare mechanical and solution kinetic data required a series of corrections to compensate for the differences in experimental conditions (0.5 M KCl, 22 degrees C for kinetic assays of myosin, 200 mM ionic strength, 12 degrees C to measure Vo). Here, a method was developed to prepare heavy meromyosin (HMM) from pure myosin isoforms isolated from single muscle fibres and to study k(-AD) (determined from the affinity of the acto-myosin complex for ADP, KAD) and the rate of ATP-induced acto-HMM dissociation (controlled by K1k+2) under the same experimental condition used to measure Vo). In fast-muscle myosin isolated from a wide range of mammalian muscles, k(-AD) was found to be too fast to limit Vo, whereas K1k+2 was of the right magnitude for ATP-induced dissociation of the cross-bridge to limit shortening velocity. The result was unexpected and prompted further experiments using the stopped-flow approach on myosin subfragment-1 (S1) and HMM obtained from bulk preparations of rabbit and rat muscle. These confirmed that the rate of cross-bridge dissociation by ATP limits the velocity of contraction for fast myosin II isoforms at 12 degrees C, while k(-AD) limits the velocity of slow myosin II isoforms. Extrapolating our data to 37 degrees C suggests that at physiological temperature the rate of ADP dissociation may limit Vo for both isoforms.     

Targeting the restricted α-subunit repertoire of airway smooth muscle GABAA receptors augments airway smooth muscle relaxation

The prevalence of asthma has taken on pandemic proportions. Since this disease predisposes patients to severe acute airway constriction, novel mechanisms capable of promoting airway smooth muscle relaxation would be clinically valuable. We have recently demonstrated that activation of endogenous airway smooth muscle GABA(A) receptors potentiates β-adrenoceptor-mediated relaxation, and molecular analysis of airway smooth muscle reveals that the α-subunit component of these GABA(A) receptors is limited to the α(4)- and α(5)-subunits. We questioned whether ligands with selective affinity for these GABA(A) receptors could promote relaxation of airway smooth muscle. RT-PCR analysis of GABA(A) receptor subunits was performed on RNA isolated by laser capture microdissection from human and guinea pig airway smooth muscle. Membrane potential and chloride-mediated current were measured in response to GABA(A) subunit-selective agonists in cultured human airway smooth muscle cells. Functional relaxation of precontracted guinea pig tracheal rings was assessed in the absence and presence of the α(4)-subunit-selective GABA(A) receptor agonists: gaboxadol, taurine, and a novel 8-methoxy imidazobenzodiazepine (CM-D-45). Only messenger RNA encoding the α(4)- and α(5)-GABA(A) receptor subunits was identified in RNA isolated by laser capture dissection from guinea pig and human airway smooth muscle tissues. Activation of airway smooth muscle GABA(A) receptors with agonists selective for these subunits resulted in appropriate membrane potential changes and chloride currents and promoted relaxation of airway smooth muscle. In conclusion, selective subunit targeting of endogenous airway smooth muscle-specific GABA(A) receptors may represent a novel therapeutic option for patients in severe bronchospasm.     

Is the nexus necessary for cell-to-cell coupling of smooth muscle?

Summary Electronmicroscopic study of electrically coupled smooth muscles was undertaken to determine the distribution of nexuses in various types of smooth muscle. The study revealed that while nexal structures were commonplace in some types of smooth muscle, they were very rare or absent in others, even though in some cases these cells were only a few nanometers distant from one another. The persistence in thin section of these structures in the main circular muscle of dog intestine after poor fixation, fixation under strain, cell shrinkage, and metabolic damage of various sorts seems to rule out the thesis that they are labile. The absence of nexuses in longitudinal muscle of dog intestine examined both by thin section and by freeze fracture suggests that in this tissue they are absent or very rarein vivo and cannot account for electrical coupling.Nexuses were discernible in thin sections of main circular muscle after a variety of experimental conditions of fixation. Metabolic inhibition orin vitro permanganate fixation partially destroyed nexal contacts. These procedures induced tissue, membrane apposition and an accompanying increase in the number of structures which resemble nexuses at low magnification (nexus-like structures). Nexus-like structures occurred in all smooth muscle fixed byin vitro permanganate associated with apposition of membranes and poor preservation of basement membrane. A technique ofin vitro permanganate fixation was developed which prevented tissue swelling; consequently nexus-like structures were absent in tissues so treated. The suggestion is made that some structures described in the literature as nexuses, following permanganate fixation, may represent nexus-like structures.The balance of evidence suggests that nexuses need not be present for electrical coupling of some smooth muscle cells, in which other types of cell-to-cell contacts must be invoked.     

History-dependent properties of skeletal muscle myofibrils contracting along the ascending limb of the force–length relationship

There is a history dependence of skeletal muscle contraction: stretching activated muscles induces a long-lasting force enhancement, while shortening activated muscles induces a long-lasting force depression. These history-dependent properties cannot be explained by the current model of muscle contraction, and its mechanism is unknown. The purposes of this study were (i) to evaluate if force enhancement and force depression are present at short lengths (the ascending limb of the force–length (FL) relationship), (ii) to evaluate if the history-dependent properties are associated with sarcomere length (SL) non-uniformity and (iii) to determine the effects of cross-bridge (de)activation on force depression. Rabbit psoas myofibrils were isolated and attached between two microneedles for force measurements. Images of the myofibrils were projected onto a linear photodiode array for measurements of SL. Myofibrils were activated by either Ca²⁺ or MgADP; the latter induces cross-bridge attachment to actin independently of Ca²⁺. Activated myofibrils were subjected to three stretches or shortenings (approx. 4% SL at approx. 0.07 µm s⁻¹ sarcomere⁻¹) along the ascending limb of the FL relationship separated by periods (approx. 5 s) of isometric contraction. Force after stretch was higher than force after shortening at similar SLs. The differences in force could not be explained by SL non-uniformity. The FL relationship produced by Ca²⁺- and MgADP-activated myofibrils were similar in stretch experiments, but after shortening MgADP activation produced forces that were higher than Ca²⁺ activation. Since MgADP induces the formation of strongly bound cross-bridges, this result suggests that force depression following shortening is associated with cross-bridge deactivation.     

Perlecan mediates the antiproliferative effect of apolipoprotein E on smooth muscle cells. An underlying mechanism for the modulation of smooth muscle cell growth?

Apolipoprotein E (apoE) is known to inhibit cell proliferation; however, the mechanism of this inhibition is not clear. We recently showed that apoE stimulates endothelial production of heparan sulfate (HS) enriched in heparin-like sequences. Because heparin and HS are potent inhibitors of smooth muscle cell (SMC) proliferation, in this study we determined apoE effects on SMC HS production and cell growth. In confluent SMCs, apoE (10 microg/ml) increased (35)SO(4) incorporation into PG in media by 25-30%. The increase in the medium was exclusively due to an increase in HSPGs (2.2-fold), and apoE did not alter chondroitin and dermatan sulfate proteoglycans. In proliferating SMCs, apoE inhibited [(3)H]thymidine incorporation into DNA by 50%; however, despite decreasing cell number, apoE increased the ratio of (35)SO(4) to [(3)H]thymidine from 2 to 3.6, suggesting increased HS per cell. Purified HSPGs from apoE-stimulated cells inhibited cell proliferation in the absence of apoE. ApoE did not inhibit proliferation of endothelial cells, which are resistant to heparin inhibition. Analysis of the conditioned medium from apoE-stimulated cells revealed that the HSPG increase was in perlecan and that apoE also stimulated perlecan mRNA expression by >2-fold. The ability of apoE isoforms to inhibit cell proliferation correlated with their ability to stimulate perlecan expression. An anti-perlecan antibody completely abrogated the antiproliferative effect of apoE. Thus, these data show that perlecan is a potent inhibitor of SMC proliferation and is required to mediate the antiproliferative effect of apoE. Because other growth modulators also regulate perlecan expression, this may be a key pathway in the regulation of SMC growth.     

Cation effects on the conformations of muscle and non-muscle α-actinins

We examined the effects of changing KCl concentration on the secondary structures of -actinins using circular dichroism (CD), 1,1-bis(4-anilino) naphthalene-5,5-disulfonic acid (bisANS) fluorescence and proteolysis experiments. Under near-physiological conditions, divalent cations also were added and changes in conformation were investigated. In 25 mm KH₂PO₄, pH 7.5, increasing KCl from 0 to 120 mm led to decreases in -helix conformation for brain, platelet and heart -actinins (40.5-30.2%, 65.5-37.8% and 37.5-27.8%, respectively). In buffered 120 mm KCl, 0.65 mm calcium produced small changes in the CD spectra of both brain and platelet -actinin, but had no effect on heart -actinin. bisANS fluorescence of all three -actinins also showed significant changes in conformation with increasing KCl. However, in buffered 120 mm KCl increasing concentrations of Ca²⁺ or Mg²⁺ did not have significant effects on the bisANS fluorescence of any -actinin. Digestion of brain, platelet and heart -actinins with -chymotrypsin showed an increase of proteolytic susceptibility in 120 mm KCl. These experiments also showed that increasing the concentration of Ca²⁺ or Mg²⁺ led to greater changes in digestion fragment patterns in the absence of KCl than in the presence of 120 mm KCl. The results suggest that -actinins exist in different conformations depending on the ionic strength of the medium, which could explain the differences in calcium and F-actin binding results obtained from different -actinins.     

Nitric oxide: Is it the cause of muscle soreness?

Skeletal muscle hosts all of the isoforms of nitric oxide synthase (NOS). It is well documented that nitric oxide (NO) regulates force generation and satellite cell activation, and therefore, damage repair of skeletal muscle. NO can also activate nociceptors of C-fibers, thereby causing the sensation of pain. Although delayed-onset of muscle soreness (DOMS) is associated with decreased maximal force generation, pain sensation and sarcomere damage, there is a paucity of research linking NO and DOMS. The present mini-review attempts to elucidate the possible relationship between NO and DOMS, based upon current literature.     

The effects of β motor stimulation on the interpretation of signals from muscle spindles

A previously proposed method for the interpretation of the signals in sensory nerve fibres is extended to incorporate activation of muscle spindles. Simulations, based on previous experimental observations, of muscle spondles subjected to ramp and hold stretches are used as input to an interpreter, where the simulated trains of action potentials are reconverted to a length change interpretation. The interpreted signals are compared with the original length change inputs to observe the effects of -stimulation and stochastic variability.