Reflex cardiovascular responses evoked by selective activation of skeletal muscle ergoreceptors

It is well known that theexercise pressor reflex (EPR) is mediated by group III and IV skeletalmuscle afferent fibers, which exhibit unique discharge responses tomechanical and chemical stimuli. Based on the difference in dischargepatterns of group III and IV muscle afferents, we hypothesized thatactivation of mechanically sensitive (MS) fibers would evoke adifferent pattern of cardiovascular responses compared with activationof both MS and chemosensitive (CS) fibers. Experiments were conductedin chloralose-urethane-anesthetized cats (n = 10).Passive muscle stretch was used to activate MS afferents, andelectrically evoked contraction of the triceps surae was used toactivate both MS and CS muscle afferents. No significant differenceswere shown in reflex heart rate and mean arterial pressure (MAP)responses between passive muscle stretch and evoked muscle contraction. However, when the reflex responses were matched according totension-time index (TTI), the peak MAP response (67 ± 4 vs.56 ± 4 mmHg, P < 0.05) was significantly greaterat higher TTI (427 ± 18 vs. 304 ± 13 kg · s, highvs. low TTI, P < 0.05), despite different modes ofafferent fiber activation. When the same mode of afferent fiberactivation was compared, the peak MAP response (65 ± 7 vs. 55 ± 5 mmHg, P < 0.05) was again predicted bythe magnitude of TTI (422 ± 24 vs. 298 ± 19 kg · s,high vs. low TTI, P < 0.05). Total sensory input fromskeletal muscle ergoreceptors, as predicted by TTI and not the modalityof afferent fiber activation (muscle contraction vs. passive stretch),is suggested to be the primary determinant of the magnitude of theEPR-evoked cardiovascular response.

     

Modulation of the soleus muscle H reflex caused by ballistic voluntary arm movements in humans

In healthy humans, we studied the influence of conditioning voluntary arm movements on the H reflex induced by transcutaneous stimulation of the tibial nerve and recorded from the soleus muscle. We examined the effects of flexion and extension of the forearm, as well as of finger clenching performed with the maximum rate. Conditioning arm movements were self-induced or realized upon presentation of a visual signal (light flash). We found that the pattern of changes in the H reflex is determined by the position of the subject’s body in the course of tests. The ipsilateral arm flexion in the elbow joint in the standing position resulted in depression of the H reflex lasting about 100 msec from the beginning of the movement, while the effect observed in the lying position (on the couch with the feet hanging free in the air) looked like a facilitation of the reflex lasting about 100 to 200 msec. The direction and dynamics of modifications of the H reflex under conditions of the use of different conditioning movements (forearm flexions/extensions and finger clenching of the ipsilateral arm, as well as contralateral forearm flexions in the elbow joint) were rather similar. We also showed that the observed facilitation of the H reflex began earlier than the voluntary arm movement (40 to 50 msec prior to the beginning). We hypothesize that these conditioning influences result from the action of central motor commands and represent the factor related to anticipatory postural rearrangements. Such rearrangements are directed toward the maintenance of equilibrium of the body in the course of a future movement. These commands depend significantly on the spatial position of the subject’s body. Neirofiziologiya/Neurophysiology, Vol. 40, No. 2, pp. 147–154, March–April, 2008.     

Tracheobronchial muscle tonus and its reflex control

Airway smooth muscle tone is reinforced during the inspiratory phase of the breathing cycle and depends largely from neurogenic motor drive carried by the vagus nerve. This muscle tone seems to be produced mostly by a vago-vagal reflex loop initiated by the tonic discharge of tracheo-bronchial and/or alveolar receptors connected to thin sensory vagal fibres (non-myelinated or C-fibres). Inhibitory influences carried by large myelinated vagal fibres connected to tracheobronchial stretch receptors and also numerous afferents from the upper airways, systemic and pulmonary circulation, digestive tract and skeletal and respiratory muscles participate to the modulation of airway tone. The identification of neurotransmitters specific of the motor or sensory pathways helps to understand the peripheral modulation of airway motor drive and also the central integration of some peripheral informations.     

Modulation of contractile activation in skeletal muscle by a calcium-insensitive troponin C mutant

Calcium controls the level of muscle activation via interactions with the troponin complex. Replacement of the native, skeletal calcium-binding subunit of troponin, troponin C, with mixtures of functional cardiac and mutant cardiac troponin C insensitive to calcium and permanently inactive provides a novel method to alter the number of myosin cross-bridges capable of binding to the actin filament. Extraction of skeletal troponin C and replacement with functional and mutant cardiac troponin C were used to evaluate the relationship between the extent of thin filament activation (fractional calcium binding), isometric force, and the rate of force generation in muscle fibers independent of the calcium concentration. The experiments showed a direct, linear relationship between force and the number of cross-bridges attaching to the thin filament. Further, above 35% maximal isometric activation, following partial replacement with mixtures of cardiac and mutant troponin C, the rate of force generation was independent of the number of actin sites available for cross-bridge interaction at saturating calcium concentrations. This contrasts with the marked decrease in the rate of force generation when force was reduced by decreasing the calcium concentration. The results are consistent with hypotheses proposing that calcium controls the transition between weakly and strongly bound cross-bridge states.     

Modulation of the masseteric reflex by gastric vagal afferents

Several investigations have shown that the vagal nerve can affect the reflex responses of the masticatory muscles acting at level either of trigeminal motoneurons or of the mesencephalic trigeminal nucleus (MTN). The present experiments have been devoted to establish the origin of the vagal afferent fibres involved in modulating the masseteric reflex. In particular, the gastric vagal afferents were taken into consideration and selective stimulations of such fibres were performed in rabbit. Conditioning electrical stimulation of truncus vagalis ventralis (TVV) reduced the excitability of the MTN cells as shown by a decrease of the antidromic response recorded from the semilunar ganglion and elicited by MTN single-shock electrical stimulation. Sympathetic and cardiovascular influences were not involved in these responses. Mechanical stimulation of gastric receptors, by means of gastric distension, clearly diminished the amplitude of twitch tension of masseteric reflex and inhibited the discharge frequency of proprioceptive MTN units. The effect was phasic and depended upon the velocity of distension. Thus the sensory volleys originating from rapid adapting receptors reach the brain stem through vagal afferents and by means of a polysynaptic connection inhibits the masseteric reflex at level of MTN cells.     

Modulation of the Aplysia gill withdrawal reflex by dopamine

The ability of dopamine to modulate gill contractions was tested in Aplysia. When dopamine was perfused through the gill vasculature, gill contractions caused by siphon stimulation (gill withdrawal reflex) and by depolarization of the gill motor neuron L7 were increased in amplitude, as compared with those evoked during seawater perfusion. Habituation of gill movements, brought about by repetitive stimulation of the siphon or of L7, was prevented by dopamine. Despite the absence of reflex habituation, the number of action potentials in central gill motor neurons, evoked by siphon stimulation, showed normal decrement. Dopamine's effects were blocked when the ctenidial nerve was cut or when L7 hyperpolarized. These data suggest that dopamine acts peripherally to increase the efficacy of L7's synaptic transmission onto gill muscle or elements of the gill neural plexus.     

Modulation of L-type Ca2+ current but not activation of Ca2+ release by the gamma1 subunit of the dihydropyridine receptor of skeletal muscle

Background

The multisubunit (α_1S,α₂-δ, β_1a and γ₁) skeletal muscle dihydropyridine receptor (DHPR) transduces membrane depolarization into release of Ca²⁺ from the sarcoplasmic reticulum (SR) and also acts as an L-type Ca²⁺ channel. To more fully investigate the function of the γ₁ subunit in these two processes, we produced mice lacking this subunit by gene targeting.

Results

Mice lacking the DHPR γ₁ subunit (γ₁ null) survive to adulthood, are fertile and have no obvious gross phenotypic abnormalities. The γ₁ subunit is expressed at approximately half the normal level in heterozygous mice (γ₁ het). The density of the L-type Ca²⁺ current in γ₁ null and γ₁ het myotubes was higher than in controls. Inactivation of the Ca²⁺ current produced by a long depolarization was slower and incomplete in γ₁ null and γ₁ het myotubes, and was shifted to a more positive potential than in controls. However, the half-activation potential of intramembrane charge movements was not shifted, and the maximum density of the total charge was unchanged. Also, no shift was observed in the voltage-dependence of Ca²⁺ transients. γ₁ null and γ₁ het myotubes had the same peak Ca²⁺ amplitude vs. voltage relationship as control myotubes.

Conclusions

The L-type Ca²⁺ channel function, but not the SR Ca²⁺ release triggering function of the skeletal muscle dihydropyridine receptor, is modulated by the γ₁ subunit.     

Modulation of semantic processing by spatial selective attention

The effects of spatial selective attention upon ERPs associated with the processing of word stimuli were investigated. While subjects maintained central eye fixation, ERPs were recorded to words presented to the left and right visual fields. In each of 6 runs, subjects focussed attention to alternate fields to perform a category-detection task. Pairs of semantically related and repeated words were embedded in the word lists presented to the attended and unattended visual fields. Consistent with prior studies, the P1-N1 visual ERP was larger when elicited by words in attended spatial locations. A large negative slow wave identified as N400 was elicited by attended, but not unattended, words. For attended words, N400 was smaller for semantically primed or repeated words. We concluded that spatial selective attention can modulate the degree to which words are processed, and that the cognitive processes associated with N400 are not automatic.     

Transient receptor potential A1 channel contributes to activation of the muscle reflex

This study was undertaken to elucidate the role played by transient receptor potential A1 channels (TRPA1) in activating the muscle reflex, a sympathoexcitatory drive originating in contracting muscle. First, we tested the hypothesis that stimulation of the TRPA1 located on muscle afferents reflexly increases sympathetic nerve activity. In decerebrate rats, allyl isothiocyanate, a TRPA1 agonist, was injected intra-arterially into the hindlimb muscle circulation. This led to a 33% increase in renal sympathetic nerve activity (RSNA). The effect of allyl isothiocyanate was a reflex because the response was prevented by sectioning the sciatic nerve. Second, we tested the hypothesis that blockade of TRPA1 reduces RSNA response to contraction. Thirty-second continuous static contraction of the hindlimb muscles, induced by electrical stimulation of the peripheral cut ends of L(4) and L(5) ventral roots, increased RSNA and blood pressure. The integrated RSNA during contraction was reduced by HC-030031, a TRPA1 antagonist, injected intra-arterially (163 ± 24 vs. 95 ± 21 arbitrary units, before vs. after HC-030031, P < 0.05). Third, we attempted to identify potential endogenous stimulants of TRPA1, responsible for activating the muscle reflex. Increases in RSNA in response to injection into the muscle circulation of arachidonic acid, bradykinin, and diprotonated phosphate, which are metabolic by-products of contraction and stimulants of muscle afferents during contraction, were reduced by HC-030031. These observations suggest that the TRPA1 located on muscle afferents is part of the muscle reflex and further support the notion that arachidonic acid metabolites, bradykinin, and diprotonated phosphate are candidates for endogenous agonists of TRPA1.     

Effects of ageing on motor unit activation patterns and reflex sensitivity in dynamic movements

Both contraction type and ageing may cause changes in H-reflex excitability. H reflex is partly affected by presynaptic inhibition that may also be an important factor in the control of MU activation. The purpose of the study was to examine age related changes in H-reflex excitability and motor unit activation patterns in dynamic and in isometric contractions. Ten younger (YOUNG) and 13 elderly (OLD) males performed isometric (ISO), concentric (CON) and eccentric (ECC) plantarflexions with submaximal activation levels (20% and 40% of maximal soleus surface EMG). Intramuscular EMG data was analyzed utilizing an intramuscular spike amplitude frequency histogram method. Average H/M ratio was always lowest in ECC (n.s.). Mean spike amplitude increased with activation level (P < .05), whereas no significant differences were found between contraction types. Both H-reflex excitability, which may be due to an increase in presynaptic inhibition, and mean spike frequency were higher in YOUNG compared to OLD. In OLD the mean spike frequency was significantly smaller in CON compared to ISO. Lack of difference in mean spike amplitude and frequency across contraction types in YOUNG would imply a similar activation strategy, whereas the lower frequency in dynamic contractions in OLD could be related to synergist muscle behavior.     

Subcellular sorting of isoactins: selective association of gamma actin with skeletal muscle mitochondria

We describe two subpopulations of actin antibodies isolated by affinity chromatography from a polyclonal antibody to chicken gizzard actin. One subpopulation recognizes gamma actins from smooth muscle and nonmuscle cells, but does not recognize alpha actin from skeletal muscle. The other subpopulation recognizes determinants that are common to alpha actin from skeletal muscle and the two gamma actin isotypes. Neither antibody recognizes cytoplasmic beta actin. Both antibodies recognize only actins or molecules with determinants that are also present in actins. By immunofluorescence we found that the anti-gamma actin colocalizes with mitochondria in fibers of mouse diaphragm, and that it does not bind detectably to the 1 bands of sarcomeres. The antibody that recognizes both alpha and gamma actins stains 1 bands intensely, as expected. We interpret these observations as preliminary evidence for selective association of gamma actin with skeletal muscle mitochondria and, more broadly, as evidence for subcellular sorting of isoactins.     

Vectorial activation of smooth muscle myosin filaments and its modulation by telokin

Smooth muscle myosin copurifies with myosin light chain kinase (MLCK) and calmodulin (CaM) as well as with variable amounts of myosin phosphatase. Therefore, myosin filaments formed in vitro also contain relatively high levels of these enzymes. Thus these filaments may be considered to be native-like because they are similar to those expected to exist in vivo. These endogenous enzymes are present at high concentrations relative to myosin, sufficient for rapid phosphorylation and dephosphorylation of the filaments at rates comparable to those observed for contraction and relaxation in intact muscle strips. The phosphorylation by MLCK/CaM complex appears to exhibit some directionality and is not governed by a random diffusional process. For the mixtures of myosin filaments with and without the endogenous MLCK/CaM complex, the complex preferentially phosphorylates its own parent filament at a higher rate than the neighboring filaments. This selective or vectorial-like activation is lost or absent when myosin filaments are dissolved at high ionic strength. Similar vectorial-like activation is exhibited by the reconstituted filament suspensions, but the soluble systems composed of isolated regulatory light chain or soluble myosin head subfragments exhibit normal diffusional kinetic behavior. At physiological concentrations, kinase related protein (telokin) effectively modulates the activation process by reducing the phosphorylation rate of the filaments without affecting the overall phosphorylation level. This results from telokin-induced liberation of the active MLCK/CaM complex from the filaments, so that the latter can also activate the neighboring filaments via a slower diffusional process. When this complex is bound at insufficient levels, this actually results in acceleration of the initial phosphorylation rates. In short, I suggest that in smooth muscle, telokin plays a chaperone role for myosin and its filaments.     

Potentiation of the exercise pressor reflex by muscle ischemia

The reflex responses to static contraction are augmented by ischemia. The metabolic "error signals" that are responsible for these observed responses are unknown. Therefore this study was designed to test the hypothesis that static contraction-induced pressor responses, which are enhanced during muscle ischemia, are the result of alterations in muscle oxygenation, acid-base balance, and K+. Thus, in 36 cats, the pressor response, active muscle blood flow, and muscle venous pH, PCO2, PO2, lactate, and K+ were compared during light and intense static contractions with and without arterial occlusion. During light contraction (15-16% of maximal), active muscle blood flow increased without and decreased with arterial occlusion (+35 +/- 12 vs. -60 +/- 11%). Arterial occlusion augmented these pressor responses by 132 +/- 25%. Without arterial occlusion, changes (P less than 0.05) were seen in PO2, O2 content, PCO2, and K+. Lactate and pH were unchanged. With arterial occlusion, changes in muscle PCO2 were augmented and significant changes were seen in pH and lactate. During intense static contraction (67-69% of maximal), muscle blood flow decreased without arterial occlusion (-39 +/- 9%) and decreased further during occlusion (-81 +/- 6%). Arterial occlusion augmented the pressor responses by 39 +/- 12%. All metabolic variables increased during contraction without arterial occlusion, but occlusion failed to augment any of these changes. These data suggest that light static ischemic contractions cause increases in muscle PCO2 and lactate and decreases in pH that may signal compensatory reflex-induced changes in arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spinal P2X receptor modulates reflex pressor response to activation of muscle afferents

Static contraction of skeletal muscle evokes increases in blood pressure and heart rate. Previous studies suggested that the dorsal horn of the spinal cord is the first synaptic site responsible for those cardiovascular responses. In this study, we examined the role of ATP-sensitive P2X receptors in the cardiovascular responses to contraction by microdialyzing the P2X receptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) into the L7 level of the dorsal horn of nine anesthetized cats. Contraction was elicited by electrical stimulation of the L7 and S1 ventral roots. Blockade of P2X receptor attenuated the contraction induced-pressor response [change in mean arterial pressure (delta MAP): 16 +/- 4 mmHg after 10 mM PPADS vs. 42 +/- 8 mmHg in control; P < 0.05]. In addition, the pressor response to muscle stretch was also blunted by PPADS (delta MAP: 27 +/- 5 mmHg after PPADS vs. 49 +/- 8 mmHg in control; P < 0.05). Finally, activation of P2X receptor by microdialyzing 0.5 mM alpha,beta-methylene into the dorsal horn significantly augmented the pressor response to contraction. This effect was antagonized by prior PPADS dialysis. These data demonstrate that blockade of P2X receptors in the dorsal horn attenuates the pressor response to activation of muscle afferents and that stimulation of P2X receptors enhances the reflex response, indicating that P2X receptors play a role in mediating the muscle pressor reflex at the first synaptic site of this reflex.     

Modulation of smooth muscle activity by catecholamines.

The inhibitory and excitatory actions of catecholamines are compared in various types of smooth muscle. Inhibition is usually but not invariably associated with membrane hyperpolarization and a decrease in membrane resistance. It also has a metabolic component frequently involving an increase in tissue cAMP. In some cases, the metabolic component is related to a cation pump, but the nature of this pump is unclear. With the exception of intestinal muscle where inhibition results from the synergistic action of alpha and beta receptors, inhibition is caused by activation of beta receptors. Excitation is mediated by alpha activation and is usually accompanied by a decrease in membrane potential and membrane resistance. Only the uterus has a metabolic component. The specific ionic permeability changes accompanying excitation are different in various smooth muscles. Clarification of the mechanisms responsible for these differential actions in various types of smooth muscle is a challenge for future work.     

Modulation of [3H]dihydropyridine receptors by activation of protein kinase C in chick muscle cells

Modulation of ion channels is an essential step for understanding the regulation of cellular functions. 1,4-Dihydropyridines (nitrendipine, nifedipine, PN 200-110, etc.) are potent inhibitors of voltage-dependent calcium channels and are important therapeutic agents in the treatment of various cardiovascular disorders such as angina and cardiac arrhythmias. In this work a new procedure is employed to determine the density of surface dihydropyridine receptors in contracting muscle cells in culture. Activation of endogenous protein kinase C (the Ca2+/phospholipid-dependent enzyme) by the tumor promoter phorbol-12-myristate or 1-oleoyl-2-acetylglycerol enhanced the number of dihydropyridine receptors without significant change in the receptor affinity. The increase in the number of receptors was associated with stimulation of the dihydropyridine-sensitive 45Ca uptake as well as activation of protein kinase C in myotubes treated with phorbol esters. These data strongly suggest that activation of protein kinase C promotes the appearance of dihydropyridine receptors in the plasma membrane.     

Trunk muscle activation during dynamic weight-training exercises and isometric instability activities

The purpose of this study was to examine the extent of activation in various trunk muscles during dynamic weight-training and isometric instability exercises. Sixteen subjects performed squats and deadlifts with 80% 1 repetition maximum (1RM), as well as with body weight as resistance and 2 unstable calisthenic-type exercises (superman and sidebridge). Electromyographic (EMG) activity was measured from the lower abdominals (LA), external obliques (EO), upper lumbar erector spinae (ULES), and lumbar-sacral erector spinae (LSES) muscle groups. Results indicated that the LSES EMG activity during the 80% 1RM squat significantly exceeded 80% 1RM deadlift LSES EMG activity by 34.5%. The LSES EMG activity of the 80% 1RM squat also exceeded the body weight squat, deadlift, superman, and sidebridge by 56, 56.6, 65.5, and 53.1%, respectively. The 80% 1RM deadlift ULES EMG activity significantly exceeded the 80% 1RM squat exercise by 12.9%. In addition, the 80% 1RM deadlift ULES EMG activity also exceeded the body weight squat, deadlift, superman, and sidebridge exercises by 66.7, 65.5, 69.3, and 68.6%, respectively. There were no significant changes in EO or LA activity. Therefore, the augmented activity of the LSES and ULES during 80% 1RM squat and deadlift resistance exercises exceeded the activation levels achieved with the same exercises performed with body weight and selected instability exercises. Individuals performing upright, resisted, dynamic exercises can achieve high trunk muscle activation and thus may not need to add instability device exercises to augment core stability training.