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Capillary configuration in contracted muscles: comparative aspects.

We compared the degree of orientation (anisotropy) of capillaries in skeletal muscles of animals with large differences in oxygen needs and/or tolerance to hypoxia (mammals of different size; reptiles; birds; mammals native to high altitude; diving mammals). In terrestrial mammals, we found a substantial increase in capillary tortuosity with fiber shortening, in muscles with large differences in capillary density (capillary counts/fiber mm2 in transverse sections ranging 450-4350). There was no systematic difference in muscle capillary tortuosity with body size (mouse to pony), or with adaptation to high altitude (deer mice) or to prolonged periods of anoxia (Harbor seals), when account was taken of sarcomere length. A substantial increase in capillary tortuosity was also found in contracted skeletal muscles of the alligator with remarkably low capillary density (capillary counts/fiber mm2 in transverse sections, 120-280). On the contrary, we found that in pigeon pectoralis, a highly aerobic muscle with large capillary density and a large number of capillary anastomoses running perpendicular to the muscle fiber axis, the decrease in capillary anisotropy with decreasing sarcomere length was smaller than in other muscles. Our results indicate that 1) sarcomere length at which samples are fixed needs to be taken into account when capillary counts in transverse sections are compared between muscles and/or after different experimental conditions, and 2) muscle capillary tortuosity is a consequence of fiber shortening, rather than an indicator of the O2 requirements of the tissue.

Alligators and Crocodiles↗

Small bowel motility: relationship between smooth muscle contraction and electroenterogram signal.

A study is made to correlate the electrical and mechanical activity of the smooth muscle of the small bowel. Bioelectrical signal recording from the intestinal serosa (electroenterogram) comprises a slow wave (SW) and spike burst (SB), though only the latter reflects intestinal pressure. The electroenterogram and smooth muscle pressure are simultaneously recorded in the canine small bowel. Spectral and time series analysis of the electroenterogram are performed to establish those electrical parameters that best reflect intestinal pressure. The results reveal an underlying correlation between the estimated parameters of electrical activity and smooth muscle pressure. In addition, parameters derived from the spectral techniques were closely correlated to pressure events in the intestine, even more so than the variables directly acquired from the classical time domain analyses. Specifically, spectral energy above 2 Hz and mean frequency (both calculated from the biosignal periodogram), are parameters that identify intestinal pressure. The extrapolation of these spectral parameters to long time periods could serve to define a motility index (MI) from electrical gut activity. In this context, electroenterogram recording and analysis can contribute to solve problems inherent to manometric recording, though the need for surgical intervention restricts electrical methods to experimental or surgical studies.

Animals↗

Ca2+-dependent and Ca2+-independent regulation of smooth muscle contraction.

An increase in the cytosolic Ca2+ concentration is a prerequisite in activation of contractile activity of smooth muscle. The shape of the Ca2+-signal is determined by spatial distribution and kinetics of Ca2+-binding sites in the cell. The increase in cytosolic Ca2+ activates myosin light chain kinase (MLCK) which in turn phosphorylates the regulatory light chains of myosin II. This Ca2+-dependent MLC20 phosphorylation is modulated in a Ca2+-independent manner by inhibiting the constitutive active myosin light chain phosphatase mediated by the monomeric GTPase Rho and the Rho-associated kinase as well as protein kinase C or by increasing its activity through cGMP. Furthermore, the activity of MLCK may be decreased due to phosphorylation by CaM kinase II and perhaps p21 activated protein kinase. Hence, smooth muscle tone appears to be regulated by a network of activating and inactivating intracellular signaling cascades which not only show a temporal but also a spatial activation pattern.

Animals↗

[Effect of imipramine and ftoracizin on platelet aggregation and smooth muscle contraction of the ureter].

The influence of the tricyclic antidepressants imipramine and ftoracizin on platelet aggregation and smooth muscle contractility was investigated in comparison with action of known smooth muscle relaxant and platelet aggregation inhibitor, papaverine. It has been shown that the tricyclic antidepressants possess potent spasmolytic activity but unlike papaverine have no effect on platelet aggregation. The biochemical mechanisms of the non-specific action of tricyclic antidepressants as well as some other structurally related-drugs are discussed.

Animals↗

Myogenic oscillatory mechanism for opossum esophageal smooth muscle contractions.

We evaluated the control of phasic contractions in opossum esophageal circular smooth muscle by determining the contractile response in vitro to agents that cause membrane depolarization and excitation by different mechanisms. Transverse muscle strips taken from different sites along the length of the smooth muscle esophagus were exposed to progressively increasing concentrations of tetraethylammonium (1-30 mM), K+ (4.6-30 mM), or bethanechol (10(-6) to 10(-2) M). In normally inactive esophageal circular smooth muscle, tetraethylammonium and high K+ concentration elicited phasic contractions that were not blocked by atropine and tetrodotoxin. Bethanechol, an M2 muscarinic receptor agonist that acts selectively on smooth muscle, elicited phasic contractions that were not blocked by tetrodotoxin. We conclude that a latent myogenic oscillatory mechanism for control of phasic contractions exists in esophageal circular smooth muscle and that it may be activated by nonspecific excitation of the smooth muscle membrane. We suggest that this myogenic oscillatory mechanism is likely excited and modulated by nerves.

Animals↗

Differences in muscle activation patterns during pelvic floor muscle contraction and Valsalva maneuver.

AIMS: To investigate the different muscle activation patterns around the abdomino-pelvic cavity in continent women and their effect on pressure generation during a correct pelvic floor muscle (PFM) contraction and a Valsalva maneuver. METHODS: Thirteen continent women were assessed. Abdominal, chest wall, and PFM activity and vaginal and intra-abdominal pressure (IAP), were recorded during two tasks: PFM contraction and Valsalva whilst bladder base position was monitored on trans-abdominal ultrasound. A correct PFM contraction was defined as one that resulted in bladder base elevation and a Valsalva resulted in bladder base depression. RESULTS: Comparison of the mean of the normalized EMG activity of all the individual muscle groups was significantly different between PFM contraction and Valsalva (P = 0.04). During a correct PFM contraction, the PFM were more active than during Valsalva (P = 0.001). During Valsalva, all the abdominal muscles (IO (P = 0.006), EO (P < 0.001), RA (P = 0.011)), and the chest wall (P < 0.001) were more active than during PFM contraction. The change in IAP was greater during Valsalva (P = 0.001) but there was no difference in the change in vaginal pressure between PFM contraction and Valsalva (P = 0.971). CONCLUSIONS: This study demonstrates a difference in muscle activation patterns between a correct PFM contraction and Valsalva maneuver. It is important to include assessment of the abdominal wall, chest wall, and respiration in the clinical evaluation of women performing PFM exercises as abdominal wall bracing combined with an increase in chest wall activity may cause rises in IAP and PFM descent.

Abdominal Wall↗

[New trends in studying the regulatory mechanism of smooth muscle contraction].

In this paper, we briefly review current topics about smooth muscle with regards to Ca2+ release, Ca2+ sensitization, and Ca2+ regulation of contraction. Inositol 1,4,5-trisphosphate releases Ca2+ from the sarcoplasmic reticulum, where Ca(2+)-dependent immediate feedback control may work. However, the involvement of this feedback control in the Ca(2+)-induced Ca2+ release mechanism remains to be elucidated. Either agonist or GTP gamma S is known to increase the Ca2+ sensitivity of myofilaments. The agonist-induced Ca2+ sensitization could be explained by the up-regulation due to myosin light chain kinase or by the down-regulation due to myosin light chain phosphatase. The GTP gamma S-induced Ca2+ sensitization seems to be mediated by rho A p21, a small G protein. Thus, myosin phosphorylation is not the obligatory way to regulate the actin-myosin interaction. We propose that cross-linking between actin and myosin may work as an alternative way to regulate the interaction from biochemical studies. The candidates for the cross-linkers are caldesmon, calponin and myosin light chain kinase. The inhibitory effect of Ca2+ on the interaction, which is observed under the specific conditions for measuring smooth muscle contraction, may hold the key to finding the physiological significance of the cross-linking activity.

Actins↗

A modified force-velocity equation for smooth muscle contraction.

It has been suggested that in skeletal muscle the force-velocity relationship may not be a simple hyperbolic one, as defined by Hill's equation. To determine whether smooth muscle demonstrated the same properties, quick-release force-velocity curves were obtained from canine tracheal smooth muscle. The results showed that the observed data points for tracheal smooth muscle systematically deviated from a hyperbola. Such deviation occurred at values of force (P) approaching maximum isometric force (Po) for curves elicited by quick release at 2 and 10 s in the course of isometric contractions. Shortening velocities under a given afterload were overestimated at the high-force end (P > 75% Po) by Hill's equation; this implied that a relationship more complex than a simple hyperbola was involved at high loads. We next focused on finding an equation to also fit those directly measured data points that did not conform to a hyperbola. Our rationale in developing the equation was that a plot of the linearized transform of Hill's equation should yield a straight line over the entire range of loads at which velocities were measured. The plot demonstrated that, in the low-load high-velocity portion of the curve, a peak value was reached at 70-80% Po, which decreased as load increased in the high-load low-velocity portion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Time course of vasodilation at the onset of repetitive skeletal muscle contractions.

To characterize the vasodilatory response in the transition from a single skeletal contraction to a series of contractions, we measured the response of hamster cremaster muscle arterioles associated with four to five skeletal muscle fibers stimulated to contract for one, two, three, or four contractions (250-ms train duration) at 4-s intervals [15 contractions per minute (CPM)] for up to 12 s, at stimulus frequencies of 4, 10, 20, 30, 40, 60, and 80 Hz. To investigate the contribution of contraction frequency, we stimulated muscle fiber bundles at 30 or 60 CPM for 12 s at stimulus frequencies of 4, 20, and 60 Hz. Arteriolar diameters at the site of overlap with the stimulated muscle fibers were measured before and after each contraction. At 15 CPM at 4, 20, and 60 Hz, we observed a peak change in diameter following the first contraction of 1.1 +/- 0.1, 1.6 +/- 0.2, and 2.1 +/- 0.2 mum that almost doubled in response to the second contraction (2.0 +/- 0.1, 3.0 +/- 0.1, and 3.8 +/- 0.1 mum, respectively), but there was no further dilation following the third or fourth contraction. A similar response occurred at all stimulus and contraction frequencies tested. At 30 and 60 CPM at 60 Hz, the plateau after two contractions was followed by a further increase in diameter to a second plateau at 7-8 s. Therefore, the vasodilatory response in the transition from single to multiple contractions had components that were stimulation parameter dependent and independent and showed a plateauing behavior indicative of rapid changes in either the nature and/or concentration of vasodilators released or changes in vascular reactivity.

Animals↗

Restoration of dysgenic muscle contraction and calcium channel function by co-culture with normal spinal cord neurons.

Muscular dysgenesis (mdg) is a spontaneous recessive lethal mutation in the mouse. The disease is characterized by a total lack of excitation-contraction coupling in embryonic skeletal muscle. This developmental abnormality is associated with a drastic deficiency in the expression of voltage-sensitive Ca2+ channels in skeletal muscle without alteration of the properties of voltage-sensitive Na+ channels or of voltage-sensitive Ca2+ channels in cardiac and neuronal cells. Membrane couplings between sarcoplasmic reticulum and the transverse tubules, known as triads, were also found to be drastically altered in embryonic muscle of the homozygous mutant (mdg/mdg). Triads in the mdg/mdg muscle were less numerous, disorganized and lacked spaced densities. This paper shows that co-culture of mdg/mdg myotubes with normal spinal cord neurons re-establishes Ca2+ channel activity, contraction and normal triad organization. The decrease thus cannot be due to a mutation of the Ca2+ channel as previously suggested. Normal nerve cells may supply an essential factor to mutant muscle cells.

Animals↗

Electrical activity in voluntarily contracting muscle.

The collision technique was used to determine the relationship between the electrical potential and the force produced by a voluntarily contracting first dorsal interosseus muscle. The method allows, in effect, synchronization of nerve impulses of asynchronously firing motoneurons subserving voluntary contraction. A compound muscle action potential, M (voluntary), thus recorded as an electrical corollary of muscle contraction, related linearly to the force of contraction under isometric conditions. Using M(voluntary), an approximate percentage of motoneuron pool discharging during a 10-msec period was calculated at various levels of voluntary effort. In ten healthy subjects, it increased linearly with muscle force from 2.4% +/- 1.4% at 0.5 kg to 23.5% +/- 9.6% at 4.5 kg.

Action Potentials↗

Role of myosin light-chain phosphorylation in guinea pig gallbladder smooth muscle contraction.

In acetylcholine (ACh)-stimulated gallbladder smooth muscle, we have previously shown that phosphorylation of the 20,000-Da myosin light chains is necessary for the initiation of contraction, that myosin is stably phosphorylated at steady state, and that dephosphorylation of cross bridges is not necessary for the slowing of cross-bridge cycling rates during the period of steady-state isometric stress. The present studies were undertaken to determine whether 1) K+ (60 or 80 mM) or cholecystokinin (CCK, 10(-8) M) stimulation is accompanied by changes in myosin light-chain phosphorylation in gallbladder smooth muscle and 2) dephosphorylated noncycling cross bridges exist in K(+)- or CCK-stimulated gallbladder smooth muscle. Isometric stress, isotonic shortening velocity, and myosin light-chain phosphorylation were determined during contraction with K+ or CCK. Steady-state isometric stress was reached within 2.5 min of stimulation with K+ or CCK and was maintained for the duration of the stimulation. Stimulation with K+ or CCK was associated with rapid increases in myosin light-chain phosphorylation and maintenance of myosin light-chain phosphorylation during the stimulation. In contrast, isotonic shortening velocity was maximal at 1 min of stimulation with either K+ or CCK and then declined significantly to values that were only 26-32% of the peak velocity. These data, along with data from previous experiments with ACh, suggest that myosin light-chain phosphorylation is essential in the initiation of contraction in gallbladder smooth muscle, regardless of the source of Ca2+ or of the contractile agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Modulation of arterial muscle contraction in Aplysia by glycine and neuron R14.

Glycine and electrical activity in neuron R14 both enhance the contractility of the anterior aorta of the gastropod Aplysia californica. Glycine and R14 do not seem to cause contraction directly, change membrane permeabilities or alter junctional potentials occurring in the muscle fibers, yet they increase the force of contractions induced by other means. Modulation of muscle contraction is a new function for glycine.

Animals↗

Rapid biphasic arteriolar dilations induced by skeletal muscle contraction are dependent on stimulation characteristics.

To test the hypothesis that measurable changes in microvasculature dilation occur in response to a single short-duration tetanic contraction, we contracted three to five skeletal muscle fibres of the hamster cremaster muscle microvascular preparation (in situ) and evaluated the response of an arteriole overlapping the active muscle fibres. Arteriolar diameter (baseline diameter = 16.4 +/- 0.9 micro m, maximum diameter = 34.7 +/- 1.2 micro m) was measured before and after a single contraction resulting from a range of stimulus frequencies (4, 10, 20, 30, 40, 60, and 80 Hz) within a 250- or 500-ms train. Four and 10 Hz produced a significant dilation at 2.9 +/- 0.4 and 6.5 +/- 2.8 s, respectively, within a 250-ms train and 3.0 +/- 0.2 and 6.1 +/- 1.3 s, respectively, within a 500-ms train. Biphasic dilations were observed within a 250-ms train at 20 Hz (at 3.9 +/- 0.9 and 22.1 +/- 4.3 s), 30 Hz (at 2.7 +/- 0.3 and 17.5 +/- 2.9 s), and 40 Hz (at 3.8 +/- 0.4 and 23.2 +/- 2.6 s) and within a 500-ms train at 20 Hz (at 4.8 +/- 0.4 and 31.9 +/- 3.8 s) and 30 Hz (at 3.4 +/- 0.3 and 27.6 +/- 3.0 s). A single dilation was observed within a 250-ms train at 60 Hz (at 5.1 +/- 0.7 s) and 80 Hz (at 14.2 +/- 3.3 s) and within a 500-ms train at 40 Hz (at 9.9 +/- 3.2 s), 60 Hz (at 7.9 +/- 2.1 s), and 80 Hz (at 13.4 +/- 4.0 s). We have shown that a single contraction ranging from a single twitch (4 Hz, 250 ms) to fused tetanic contractions produces significant arteriolar dilations and that the pattern of dilation is dependent on the stimulus frequency and train duration.

Animals↗

Force and motion generation of myosin motors: muscle contraction.

Brownian ratchet theory refers to the phenomenon that non-equilibrium fluctuations in an isothermal medium and anisotropic system can induce mechanical force and motion. This concept of noise-induced transport has motivated an abundance of theoretical and applied research. One of the exciting applications of the ratchet theory lies in the possible explanation of the operating mode of biological molecular motors. Biomolecular motors are proteins able of converting chemical reactions into mechanical motion and force. Operating at energy levels only a few times greater than the energy levels of thermal baths, their operating mode has to be stochastic in nature. Here, we review the theoretical concepts of the Brownian ratchet theory and its possible link to the operation of the myosin II motors involved in muscle contraction.

Adenosine Triphosphate↗