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At least 883 records · Page 49Linked to original sources

Inhibition of fundic strips from guinea-pig stomach: the effect of theophylline on the membrane potential, muscle contraction and ion fluxes.

The effect of theophylline on the smooth muscle cells of the fundic part of the stomach of the guinea pig was investigated. Theophylline hyperpolarized the membrane, inhibited spike discharges and slow waves and produced relaxation of the muscle cells. Furthermore, the theophylline-induced relaxation was not affected in low sodium solution or during inhibition of the sodium pump. Partial inhibition of the theophylline relaxation was seen in muscle depolarized by a high potassium solution and also when ATP was the relaxant. The potassium efflux was enhanced by ATP, but was not markedly changed by theophylline. A change in calcium efflux in the presence of theophylline could not be measured in quiescent preparations. The calcium influx was not changed by theophylline in Krebs, by low Ca, or by high K solution. Furthermore, the tissue content of cyclic AMP was increased by 59.6% in the presence of theophylline (2 x 10(-3) M). The conclusion is reached that the most likely mode of action of theophylline is a suppression of spontaneous activity and an extensive calcium binding to internal sites.

Animals↗

Myosin light chain kinase and myosin phosphorylation effect frequency-dependent potentiation of skeletal muscle contraction.

Repetitive stimulation potentiates contractile tension of fast-twitch skeletal muscle. We examined the role of myosin regulatory light chain (RLC) phosphorylation in this physiological response by ablating Ca(2+)/calmodulin-dependent skeletal muscle myosin light chain kinase (MLCK) gene expression. Western blot and quantitative-PCR showed that MLCK is expressed predominantly in fast-twitch skeletal muscle fibers with insignificant amounts in heart and smooth muscle. In contrast, smooth muscle MLCK had a more ubiquitous tissue distribution, with the greatest expression observed in smooth muscle tissue. Ablation of the MYLK2 gene in mice resulted in loss of skeletal muscle MLCK expression, with no change in smooth muscle MLCK expression. In isolated fast-twitch skeletal muscles from these knockout mice, there was no significant increase in RLC phosphorylation in response to repetitive electrical stimulation. Furthermore, isometric twitch-tension potentiation after a brief tetanus (posttetanic twitch potentiation) or low-frequency twitch potentiation (staircase) was attenuated relative to responses in muscles from wild-type mice. Interestingly, the site of phosphorylation of the small amount of monophosphorylated RLC in the knockout mice was the same site phosphorylated by MLCK, indicating a potential alternative signaling pathway affecting contractile potentiation. Loss of skeletal muscle MLCK expression had no effect on cardiac RLC phosphorylation. These results identify myosin light chain phosphorylation by the dedicated skeletal muscle Ca(2+)/calmodulin-dependent MLCK as a primary biochemical mechanism for tension potentiation due to repetitive stimulation in fast-twitch skeletal muscle.

Animals↗

Crossbridge phosphorylation and regulation of vascular smooth muscle contraction.

A model is proposed to explain crossbridge regulation in smooth muscle and the latch state (high force with very low crossbridge cycling rates). The model predicts that low levels of [Ca2+] and myosin phosphorylation can induce high values of force. In this analysis we show that reductions in myosin light chain phosphatase activity make stress more proportional to phosphorylation, with abolition of the latch state. This may explain some of the differences in the phosphorylation dependence of force between intact and skinned smooth muscle.

Animals↗

High-speed cinematography of muscle contraction.

Motion pictures of the "twitch" of an excised frog gastrocnemius muscle taken at rates of 6000 frames per second provide a means of very accurately timing the phases. The extreme "slow motion" reveals surface phenomena not observable by other techniques. Evidence of "active relaxation" is suggested by results of frame-by-frame analysis.

Humans↗

Inspiratory action of separate external and parasternal intercostal muscle contraction.

We have previously shown that electrical stimulation of the thoracic spinal cord produces near maximal activation of the inspiratory intercostal muscles. In the present investigation, we used this technique to evaluate the relative capacity of separate external (EI) and parasternal intercostal (PA) muscle contraction to produce changes in airway pressure and inspired volume. Studies were performed in 23 anesthetized phrenicotomized dogs. Electrical stimuli were applied to the spinal cord after hyperventilation-induced apnea, before and after sequentially severing either the PA or EI muscles from the first through sixth intercostal spaces. During spinal cord stimulation (SCS), measurements were made of inspired volume (delta V) with the airway open and negative airway pressure (delta P) during tracheal occlusion. Compared with control values, sectioning of the PA muscles resulted in a 40.9% reduction in delta P and 35.7% reduction in delta V during SCS. In other animals, initial sectioning of the EI muscles produced reductions in delta P and delta V of 67.4 and 63.0, respectively, during SCS. After subsequent section of the PA muscles, SCS produced only negligible inspired volumes and changes in airway pressure. We conclude that 1) the EI and PA muscles are each capable of generating substantial changes in airway pressure and large inspired volumes and 2) the ventilatory capacity of the EI muscles exceeds that of the PA muscles.

Animals↗

Studies of ent-kaurane diterpenes from Oyedaea verbesinoides for their inhibitory activity on vascular smooth muscle contraction.

From the aerial parts of Oyedaea verbesinoides nine ent-kauranes and a sesquiterpene were isolated. ent-9alpha-Hydroxy-kaur-16-en-19-oic acid, ent-15beta-tigloyloxy-9alpha-hydroxy-kaur-16-en-19-oic acid, ent-15beta-angeloyloxy-9alpha-hydroxy-kaur-16-en-19-oic acid, ent-16alpha-hydroxykaurane and 1alpha-angeloyloxy-carotol are new for the genus or the species and ent-15beta-angeloyloxy-7alpha,9alpha-dihydroxy-kaur-16-en-19-oic acid is reported for the first time. Structure elucidation was based on one and two dimensional NMR as well as ESI and CI-MS analysis. Some diterpenes were proven to exhibit inhibitory effects on smooth muscle contraction on rat aorta.

Animals↗

[The role of sarcolemma calcium pump in regulating tonic smooth muscle contraction].

Vanadate (10(-4)-10(-3) M) effectively blocks Mg2+, ATP-dependent Ca2+ transport in sarcolemmal vesicles and induces a slowly tonic contraction of the smooth muscle. This contraction was observed both with and without nifedipine (10(-5) M) evoking complete inhibition of hyperpotassium contracture, the Ca2+ removal from the solution washing the muscular preparation stimulating the tone decrease. There is a close correlation between the dose-dependent effects of vanadate on the Ca pump activity and tension. It is concluded that in smooth muscles, at least in myometrium, the sarcolemmal Ca-pump is involved into the control of the tonic tension.

Adenosine Triphosphate↗

Kinaesthetic signals and muscle contraction.

Signals generated both peripherally and centrally contribute to the group of sensations termed kinaesthesia. Many experiments report sensations of position and movement under passive relaxed conditions without muscle contraction. However, kinaesthetic acuity is probably of greater functional value when subjects are active rather than passive and, accordingly, movement detection is markedly improved by muscular contraction. One mechanism contributing to this enhancement is likely to involve muscle spindle volleys. When identical microstimulation techniques are applied to skin, joint and muscle spindle endings innervating the hand, some cutaneous afferents and some joint afferents elicit a sensation, but activation of certain other cutaneous afferents and muscle spindle afferents rarely does. Activity in more than one muscle spindle afferent may be required for kinaesthetic sensations, whereas some single cutaneous and joint afferents may have a more 'secure' central projection.

Animals↗

Discharge of red nucleus neurons during voluntary muscle contraction: activity patterns and correlations with isometric force.

Discharges of red nucleus neurons were analyzed in the cat during voluntary muscle contractions performed under isometric and anisometric conditions. The observations established: (1) that neurons of the red nucleus modulate their firing in advance of the motor output under both conditions; (2) that increased activity of these neurons is specific to the direction of the force exerted ; (3) that this increase is primarily related to the magnitude of the rate of force change generated by the animal.

Action Potentials↗

Urinary trypsin inhibitor prevents uterine muscle contraction by inhibition of Ca++ influx.

OBJECTIVE: The aim of this research was to elucidate the mechanism of action of urinary trypsin inhibitor, a Kunitz-type protease inhibitor, in suppressing uterine muscle contraction. STUDY DESIGN: An isometric uterine contraction test was used to study this inhibitory effect of urinary trypsin inhibitor on the myometrium. Oxytocin, prostaglandin F2 alpha, and lipopolysaccharide were used to stimulate myometrial contraction. Prostaglandins F2 alpha and E2 were measured in the buffer solution. Influx of calcium into uterine smooth muscle cells was assessed by digital imaging microscopy. RESULTS: After incubation with urinary trypsin inhibitor or fetal urine, myometrial contractions stimulated by oxytocin, prostaglandin F2 alpha or lipopolysaccharide were suppressed completely. The concentrations of prostaglandins F2 alpha and E2 in the buffer solution during the isometric contraction test were significantly increased by lipopolysaccharide stimulation, but when urinary trypsin inhibitor was present in the buffer solution the concentrations of prostaglandins F2 alpha or E2 did not change significantly. Preincubation with urinary trypsin inhibitor also inhibited calcium influx, resulting in no detectable change in the intracellular free calcium concentration of smooth muscle cells. CONCLUSION: We proposed that urinary trypsin inhibitor from fetal urine inhibits uterine muscle contraction by regulation of intracellular Ca++.

Calcium↗

Two elementary models for the regulation of skeletal muscle contraction by calcium.

It is shown by use of an extremely simple explicit two-state model that two basic ideas may be sufficient to understand at least qualitatively the sensitive activation of isometric muscle contraction by Ca2+. (a) Ca2+ binds much more strongly on troponin if myosin is already attached to actin. The steady state analogue of this is that the single rate constant (in the two-state model) for myosin attachment plus Pi release is much larger if Ca2+ is bound to troponin. (b) End-to-end tropomyosin interactions are responsible for positive cooperativity. Although these ideas seem to be sufficient, this of course does not mean that they are necessary. These same ingredients were used in two previous, more elaborate models for the cooperative equilibrium binding of myosin subfragment-1 on actin-tropomyosin-troponin, with and without Ca2+, and for a study of the steady state ATPase activity of the same system. Essentially as an appendix, the above-mentioned simple treatment is extended to a somewhat more realistic and complicated model of isometric contraction.

Adenosine Triphosphate↗

Effects of stapedius-muscle contractions on the masking of auditory-nerve responses.

There has been little exploration of the mechanisms by which stapedius muscle contractions reduce the masking of responses to high-frequency sounds by low-frequency sounds. To fill this gap in knowledge, controlled stapedius contractions were elicited with direct shocks in anesthetized cats, and measurements were made of the effects of these contractions on the masking of single auditory-nerve fibers and on the attenuation of middle-ear transmission. The results show that the stapedius-induced reductions of masking can be much larger than the attenuations of low-frequency sound. With a 300-Hz band of masking noise centered at 500 Hz, and signal tones at 6 or 8 kHz, unmasking effects over 40 dB were observed for sounds 100 dB SPL or less. The data suggest that much larger unmasking might occur. The observed unmasking can be explained completely by a linear stapedius-induced attenuation of sound transmission through the middle ear and a nonlinear growth rate of masking for auditory-nerve fibers. No central effects are required. It is argued that the reduction of the upward spread of masking is probably one of the most important functions of the stapedius muscle.

Acoustic Stimulation↗

In vitro generation of smooth muscle-contracting leukotrienes from isolated epidermal cells.

Single-cell suspensions of murine and human epidermal cells were studied for the presence of peptidoleukotrienes (LTs), using in vitro guinea pig ileum contraction as bioassay and a commercial radioimmunoassay. The calcium ionophore A23187 at 5 x 10(-6) M alone or in combination with arachidonic acid at 10(-4) M caused release of LTC4/D4 within 10-30 min and for up to 18 h. LTB4, as was measured in the chemotaxis assay, was released at different levels and with different kinetics from the same cells. Epidermal cells may thus regulate cutaneous inflammation by secreting potent vasoactive and muscle-contracting in addition to chemotactic lipid mediators.

Animals↗

Actin as the generator of tension during muscle contraction.

We propose that the key structural feature in the conversion of chemical free energy into mechanical work by actomyosin is a myosin-induced change in the length of the actin filament. As reported earlier, there is evidence that helical actin filaments can untwist into ribbons having an increased intersubunit repeat. Regular patterns of actomyosin interactions arise when ribbons are aligned with myosin thick filaments, because the repeat distance of the myosin lattice (429 A) is an integral multiple of the subunit repeat in the ribbon (35.7 A). This commensurability property of the actomyosin lattice leads to a simple mechanism for controlling the sequence of events in chemical-mechanical transduction. A role for tropomyosin in transmitting the forces developed by actomyosin is proposed. In this paper, we describe how these transduction principles provide the basis for a theory of muscle contraction.

Actins↗

Induction of enhanced release of endothelium-derived relaxing factor after prolonged exposure to alpha-adrenergic agonists: role in desensitization of smooth muscle contraction.

Desensitization of alpha 1-adrenergic receptor-mediated contraction occurs in rat aorta after in vitro exposure to alpha-adrenergic agonists; we previously showed that a component of the desensitization is endothelial cell dependent. Our primary purpose was to examine possible alterations in either the release or action of endothelium-derived relaxing factor (EDRF) in desensitized blood vessels. Rings of rat aorta were desensitized in vitro by exposure to phenylephrine (PE) for 6 h with impaired subsequent ability of PE to induce smooth muscle contraction. PE also induced heterologous desensitization of serotonin-induced contraction, which was blocked by the alpha 1-adrenergic selective antagonist prazosin. Using a "sandwich" bioassay technique, we noted enhanced release of EDRF from the aortic rings that had been previously exposed to PE as compared with controls. The capacity of PE to activate accumulation of inositol monophosphate was impaired in the desensitized blood vessels, both with and without endothelium. Our results suggest that prolonged exposure to alpha-adrenergic agonists leads to several adaptations in vascular smooth muscle (VSM), including enhanced release of EDRF. Although impaired action of EDRF has been suggested to play a role in diseases such as diabetes and atherosclerosis, our results indicate that release and action of EDRF may be enhanced with prolonged exposure to alpha-agonists.

Adrenergic alpha-Agonists↗

Modeling of cardiac muscle contraction based on the cross-bridge mechanism.

A mathematical model was developed for the cardiac muscle contraction, assuming that the attachment and detachment cycle of the cross-bridge is activated by the internal calcium concentration and the rate constant of the cycle depends on the sliding velocity of myofilaments. The inputs of the model are the rates of calcium release and uptake, while the output is the tension curve of the muscle. The variables are factored into a series of realizable functions and most constants were determined from the dynamic constants for the tetanic contraction of frog ventricular muscle at 20 degrees C. Using this model, the calcium transient curve as well as the change in the number of cross-bridges in each state of the cycle during a given experimental twitch tension curve was calculated with a PDP 11/60 computer, by selecting the input parameters so that the output curve fit the experimental curve. When the twitch tension was increased by increasing initial muscle length, the rate of calcium release increased and that of uptake decreased. At higher external calcium concentrations, the similar changes in the input parameters were observed. In the presence of 5 X 10(-6) g/ml adrenaline the duration of activation was markedly prolonged, while the rates of calcium release and uptake show little change.

Animals↗

Hugh E. Huxley: birth of the filament sliding model of muscle contraction.

Hugh E. Huxley used a combination of X-ray diffraction and electron microscopy to define the structural basis for muscle contraction. He developed the entirely new concept of movement based on the relative motion of two elongated protein polymers powered by the action of independent molecular motors. The concept applies to a large number of cell motility mechanisms.

Animals↗

Sound generation in the searobin (Prionotus carolinus), a fish with alternate sonic muscle contraction.

The Northern searobin (Prionotus carolinus) contracts its paired sonic muscles alternately rather than simultaneously during sound production. This study describes this phenomenon and examines its effect on sound production by recording sound and EMGs during voluntary and electrically stimulated calls. Sounds produced by a single twitch resulted in a two-part sound representing contraction and relaxation sounds. The relaxation sound of one twitch coincides with the contraction sound of the next twitch of that muscle. Maximum amplitude of evoked sounds occurs between 100 Hz and 140 Hz, approximately half the fundamental frequency of a voluntarily calling fish. The muscle is capable of following electrical stimulation at frequencies of up to 360 Hz. Rapid damping and response over a wide frequency range indicate that the swimbladder is a highly damped, broadly tuned resonator. A consequence of alternate contraction is a 3.3 dB loss in acoustic pressure due to the contraction of a single sonic muscle at a time. This decrease in amplitude is offset by a doubling of fundamental frequency and a constructive interaction between the sides of the bladder, resulting in increased amplitude of each unilaterally produced sound. The alternate contraction of the bilateral sonic muscles represents a novel solution to the inherent trade-off between speed and force of contraction in rapidly contracting sonic muscles.

Air Sacs↗