The physiology of the mammalian urinary outflow tract

Urinary outflow from the mammalian bladder occurs through the urethra. This outflow tract is a complicated structure composed of striated and smooth muscle and vascular urothelium. It is controlled by somatic and autonomic nerves and has several functions: it generates sustained tone to prevent urinary leakage during bladder filling; it generates transient reflex increases in pressure to prevent opening of the lumen when abdominal pressure rises; it undergoes relaxation preceding micturition and can generate urethral opening and shortening during micturition. A urethral pressure profile shows a peak pressure of > or = 100 cmH2O. The outermost coat is striated muscle, the striated or external sphincter. The fibres are predominantly circularly oriented. The extent varies in different species and between sexes. In the human female it extends the length of the urethra, and is composed mainly of slow twitch fibres. In the male, the sphincter extends from the membranous urethra over the base of the prostate and has nearly equal numbers of slow and fast twitch fibres. In both sexes, the posterior border may be deficient in striated muscle, and filled by circularly oriented smooth muscle. Activity in the slow twitch fibres through somatic nerves may be continuous during bladder filling. Outer circular and inner longitudinal smooth muscle is present Strips from either layer will generate sustained tone particularly if dissected from the high pressure zone. This tone is myogenic, and may be achieved in the absence of action potentials, but relies on influx of calcium through L-type calcium channels. Both layers receive sympathetic and parasympathetic excitatory innervation and nitrergic inhibitory innervation. Normal urethral pressure requires blood flow to the urothelium (lamina propria). Striated and smooth muscles are both thought to contribute to the resting urethral pressure in the human. The precise role of the smooth muscles during micturition is as yet unresolved.     

家兔Onuf核及其相关神经元的对照观察

以会阴肌及阴部神经注射为实验组,直肠、盆神经及坐骨神经注射为对照组,以HRP法在家兔骶尾髓白,对Onuf核及其相关神经元进行对照观察。分析了家兔Onuf核及其神经元的特点,提出了盆脏平滑肌与会阴横鈫肌功能密切的骶尾髓内神经机制。     

The Distribution of Muscles Fibers and Their Types in the Female Rat Urethra: Cytoarchitecture and Three‐Dimensional Reconstruction

An attempt to explore urethral cytoarchitecture including the distribution of smooth muscles and fast and slow striated muscles of adult female Sprague Dawley rat—a popular model in studying lower urinary tract function. Histological and immunohistochemical stainings were carried out to investigate the distribution of urethral muscle fibers and motor end plates. The urethral sphincter was furthermore three‐dimensionally reconstructed from serial histological sections. The mucosa at the distal urethra was significantly thicker than that of other segments. A prominent inner longitudinal and outer circular layer of smooth muscles covered the proximal end of urethra. Thick circular smooth muscles of the bladder neck region (urethral portion) decreased significantly distalward and longitudinal smooth muscles became 2‐ to 3‐fold thicker in the rest of the urethra. An additional layer of striated muscles appeared externally after neck region (urethra) and in association with motor end plates ran throughout the remaining urethra as the striated sphincter layer. Most striated muscles were fast fibers while relatively fewer slow fibers often concentrated at the periphery. A pair of extraneous striated muscles, resembling the human urethrovaginal sphincter muscles, connected both sides of mainly the distal vagina to the dorsal striated muscles in the wall of the middle urethra. The tension provided by this pair of muscles, and in conjunction with the striated sphincter of the urethral wall, was likely to function to suspend the middle urethra and facilitates its closure. Comprehensive morphological data of urethral sphincter offers solid basis for researchers conducting studies on dysfunction of bladder outlet. Anat Rec, 296:1640–1649, 2013. © 2013 Wiley Periodicals, Inc.     

Morphological and certain histochemical changes in striated muscle in various forms of denervation

Summary A study was made on the cat tongue tissues, in particular the striated muscles, in various types of denervation. The material was examined by histological and some other histochemical methods in terms ranging from 2 to 60 days. The sensory denervation was characterized by the development in the deafferentated region of an inflammatory process accompanied by a decrease in the degree of maturity of highly differentiated tissue structures. The motor denervation caused atrophy of the striated muscles, their destruction and replacement by connective tissue. Desympathization had no effect on the structure of the straited muscles, but caused the destruction of the smooth muscles of the walls of certain vessels.(Presented by Active Member of USSR Academy of Medical Sciences, V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 60, No. 8, pp. 115–117, August, 1965     

Myositis in mice inoculated with Borrelia burgdorferi.

The authors describe the appearance of myositis in immunocompetent and immunodeficient mice after subcutaneous inoculation with Borrelia burgdorferi by histology and immunohistology. Experimental infection of mice 1) causes inflammation of striated but not smooth muscles, 2) affects the entire musculoskeletal system, and 3) is characterized by perivascular and interfacicular infiltration of mononuclear leukocytes in the striated muscle leading to necrosis as well as disruption of muscle fibers. The lesions found in striated muscle specimens were most pronounced in immunodeficient (SCID), less severe in T-cell-deficient nu/nu (BALB/c, C57BL/6) and marginal to moderate or almost not present in immunocompetent AKR/N and C.B-17 mice, respectively.     

Site-dependent differences in density of sympathetic nerve fibers in muscle-innervating nerves of the human head and neck

The autonomic nerve supply of skeletal muscle has become a focus of interest because it is closely related to the adaptation of energy metabolism with aging. We have performed an immunohistochemistry study on tyrosine hydroxylase (TH) and neuronal nitric oxide synthase (nNOS) using specimens obtained from ten selected elderly cadavers (mean age 83.3 years) in which we examined muscle-innervating nerves (abbreviated “muscle-nerves” hereafter) of ten striated muscles (soleus, infraspinatus, extra-ocular inferior rectus, lateral rectus, superior obliquus, temporalis, orbicularis oculi, posterior cricoarytenoideus, trapezius and genioglossus) and, as a positive control, the submandibular ganglion. We found that the extra-ocular muscles received no or very few TH-positive nerve fibers. Muscle-nerves to the other head and neck muscles contained a few or several TH-positive fibers per section, but their density (proportional area of TH-positive fibers per nerve cross-section) was one-half to one-third of that in nerves to the soleus or infraspinatus. We did not find nNOS-positive fibers in any of these muscle-nerves. In the head and neck muscles, with the exception of those of the tongue, there appeared to be very few TH-positive nerve fibers along the feeding artery. Consequently, the head and neck muscles seemed to receive much fewer sympathetic nerves than limb muscles. There was no evidence that nNOS-positive nerves contributed to vasodilation of feeding arteries in striated muscles. This site-dependent difference in sympathetic innervation would reflect its commitment to muscle activity. However, we did not find any rules determining the density of nerves according to muscle fiber type and the mode of muscle activity.     

Mini-titins in striated and smooth molluscan muscles: structure,location and immunological crossreactivity

Summary Invertebrate mini-titins are members of a class of myosin-binding proteins belonging to the immunoglobulin superfamily that may have structural and/or regulatory properties. We have isolated mini-titins from three molluscan sources: the striated and smooth adductor muscles of the scallop, and the smooth catch muscles of the mussel. Electron microscopy reveals flexible rod-like molecules about 0.2 m long and 30 Å wide with a distinctive polarity. Antibodies to scallop mini-titin label the A-band and especially the A/I junction of scallop striated muscle myofibrils by indirect immunofluorescence and immuno-electron microscopy. This antibody crossreacts with mini-titins in scallop smooth and Mytilus catch muscles, as well as with proteins in striated muscles from Limulus, Lethocerus (asynchronous flight muscle), and crayfish. It labels the A/I junction (I-region in Lethocerus) in these striated muscles as well as in chicken skeletal muscle. Antibodies to the repetitive immunoglobulin-like regions and also to the kinase domain of nematode twitchin crossreact with scallop mini-titin and label the A-band of scallop myofibrils. Electron microscopy of single molecules shows that antibodies to twitchin kinase bind to scallop mini-titin near one end of the molecule, suggesting how the scallop structure might be aligned with the sequence of nematode twitchin.     

Gene expression analyses of essential catch factors in the smooth and striated adductor muscles of larval, juvenile and adult great scallop (Pecten maximus)

The scallop adductor muscle consists of striated fibres responsible for the fast closure of the shells, and smooth fibres able to maintain tension in a prolonged state of contraction called catch. Formation of the force-bearing catch linkages has been demonstrated to be initiated by dephosphorylation of the key catch-regulating factor twitchin by a calcineurin-like phosphatase, while the involvement of other thick filament proteins is uncertain. Here we report on the development of catchability of the adductor smooth muscle in the great scallop (Pecten maximus) by analysing the spatio-temporal gene expression patterns of the myosin regulatory light chain (MLCr), twitchin, myorod and calcineurin using whole mount in situ hybridization and real-time quantitative PCR. The MLCr signal was identified in the retractor and adductor muscles of the pediveliger larvae, and the juvenile and adult scallop displayed abundant mRNA levels of MLCr in the smooth and striated adductor muscles. Twitchin was mainly expressed in the smooth adductor muscle during metamorphosis, whereas the adult striated adductor muscle contained seven-folds higher twitchin mRNA levels compared to the smooth portion. Calcineurin expression predominated in the gonads and in the smooth adductor, and five-folds higher mRNA levels were measured in the smooth than in the striated fibres at the adult stage. In contrast to the other genes examined, the expression of myorod was confined to the smooth adductor muscle suggesting that myorod plays a permissive role in the molluscan catch muscles, which are first required at the vulnerable settlement stage as a component of the predator defence system.     

Morphology and Innervation of the Human Cremaster Muscle in Relation to its Function

The electromyographic properties of the cremaster muscle (CM) are quite different from other skeletal muscles. It shows excessive spontaneous discharges, and the motor unit shape and firing frequency of the CM muscle differ from that of limb muscles. In this study, CM of six adult cadavers and six orchiectomy specimens were used to reveal the detailed histology of the muscle and provide an anatomophysiological explanation for these unusual electromyographic properties. Routine histochemical stains revealed the CM was composed of several distinct bundles of smooth and striated muscle fibers within connective tissue. The smooth muscle fibers that were more profuse than previously known and were not arranged in layers, but widely dispersed between striated muscle fibers. Bielschowsky silver staining technique, anti‐neurofilament and anti‐synaptophysin immunostaining showed the presence of multiple motor end‐plates observed as a series of small dots or lines running along the striated muscle fibers and several nerve endings on a single muscle fiber. Myosin immunostaining confirmed the CM is a slow‐twitch muscle, and α‐actin smooth muscle immunostaining confirmed the presence of a large number of smooth muscle fibers. There were also small multipolar neurons forming nerve plexuses between smooth muscle fibers. Anti‐GFAP immunostaining confirmed the presence of glial cells similar to astrocytes. In conclusion, the findings of this detailed anatomical study showed the CM, widely known as a striated muscle, contains a large number of smooth muscle fibers, and the spontaneous electromyographic discharges are due to the presence of multiple motor end‐plates and dense innervation. Anat Rec,291:790‐796, 2008. © 2008 Wiley‐Liss, Inc.     

Direct and indirect effects of histamine on the smooth muscle cells of the guinea-pig main pulmonary artery

Electrophysiological studies of the effects of histamine on the smooth muscles in the guinea-pig main pulmonary artery revealed that this amine produced muscle contraction with an associated depolarization of the membrane. Application of cimetidine potentiated and that of mepyramine suppressed these histamine-induced responses. In the presence of mepyramine, histamine produced membrane hyperpolarization. Contractions produced by perivascular nerve stimulation were potentiated by histamine, and additional application of cimetidine further potentiated while addition of mepyramine suppressed the histamine-induced enhancement. The amplitude of excitatory junction potentials was increased by application of histamine plus cimetidine and was decreased by histamine plus mepyramine. Excitatory effects of histamine on the electrical and mechanical responses were reduced by application of tetrodotoxin, prazosin, phentolamine or guanethidine. In the presence of these drugs, histamine produced depolarization with an associated increase in membrane resistance and, in high concentrations, produced spike potentials. Electrical and mechanical responses of the smooth muscles to exogenously applied noradrenaline were potentiated by pretreatment with histamine and cimetidine, and were suppressed by histamine and mepyramine. These observations indicate that the guinesa-pig main pulmonary artery possesses two types of histamine receptor, H₁- and H₂-receptors, in the smooth muscles and in the perivascular adrenergic nerves. Stimulation of H₁ or H₂-receptor produces excitatory or inhibitory effects, respectively, on the smooth muscles and on the adrenergic nerves. Contraction of the muscle tissues produced by histamine is brought about by a direct effect on the smooth muscles and by increased release of transmitters, as a result of excitation of perivascular nerves.     

Function and distribution of beta3-adrenoceptors in rat, rabbit and human urinary bladder and external urethral sphincter.

1. Activation of beta-adrenoceptors causes relaxation of the urinary bladder and contraction of the external urethral sphincter, which consists of fast-contracting skeletal muscles. A beta2-adrenoceptor agonist, clenbuterol, recently has been developed as a therapeutic drug for the treatment of urinary incontinence, however beta2-adrenoceptor agonists have undesirable effects on cardiac and striated muscle function. 2. In this study, we compared the effects of the beta2-adrenoceptor agonist, clenbuterol and of a novel beta3-adrenoceptor agonist, GS332, on urinary bladder and external urethral sphincter function in rat, rabbit and human. We also determined the distribution of beta3-adrenoceptors in human urinary bladder and external urethral sphincter, using radioligand-binding techniques. 3. Clenbuterol induced marked relaxations in rat, rabbit and human urinary bladder smooth muscles and also induced marked contractions in rat periurethral striated muscles (external urethral sphincter), while GS332 induced marked relaxations in rat and human, but not in rabbit, urinary bladder smooth muscles and induced small contractions in rat periurethral striated muscles. 4. The radioligand binding studies showed presence of beta2- and beta3-adrenoceptors in human urinary bladder, external urethral sphincter and abdominal rectus muscles. The affinities of GS332 were the highest in urinary bladder and the lowest in the skeletal (abdominal rectus) muscles, while the affinities of clenbuterol were similar in urinary bladder, external urethral sphincter and the skeletal (abdominal rectus) muscles. 5. These results suggest that GS332 could, similarly clenbuterol, have a role in the treatment of urinary frequency and urinary incontinence.     

Anatomical and physiological characteristics of perineal muscles in the female rabbit

Little information is available on the participation of the perineal striated muscles in female reproductive processes. Here, we describe the gross anatomy and innervation of two striated perineal muscles in the female rabbit, the bulbospongiosus (BSM) and ischiocavernosus (ISM), and analyze their reflex electromyographic (EMG) activity in response to stimulation of the perigenital skin and vaginal tract. Twenty-four mature chinchilla-breed rabbit does were used: 12 to describe the anatomy and innervation of the muscles, 9 to determine reflex EMG activity of the muscles in response to stimulation of the perigenital skin and specific levels of the vaginal tract and 3 to analyze the effect of contraction of the muscles on intravaginal pressure. Both muscles were well developed, with their fibers originating at the ischiadic arch and inserting onto the ligamentum suspensorium clitoridis. Branches of the clitoral and perineal nerves innervated the BSM and ISM, respectively. Bilateral electrical stimulation of these nerves provoked retraction of the clitoral sheath and an increase in intravaginal pressure at the level of the perineal vagina. Whereas neither muscle responded to stimulation of the perigenital skin, both were reflexively activated during mechanical stimulation of the inner walls of the perineal vagina. Prolonged cervical stimulation inhibited this reflex. Thus, in reproductive processes such as copulation and/or parturition, the contraction of these muscles may be induced during stimulation of the perineal vagina.     

Immunohistochemical evidence for the presence of protein kinase C beta-subtype in rat motoneurons and myoneural junctions

The localization of protein kinase C beta-subtype-like immunoreactivity (PKC-beta-LI) was studied in the spinal cord and in different striated muscles of rat. In the spinal cord, large motoneurons in the ventral horn were PKC-beta-immunoreactive (IR). Strong immunoreactivity to PKC-beta was found in large nerve bundles between muscles, and in smaller nerves among muscle fibers. Myoneural junctions, which showed weaker immunoreactivity to PKC-beta, were also demonstrated in all muscles studied; the external ocular muscles, the diaphragma and the triceps surae muscle. Muscle cells were not labelled.     

Enteric neuromuscular junctions: comparison of ultrastructural features in different phylogenetic groups

The enteric neuromuscular junctions of snail (Helix pomatia), locust (Locusta migratoria migratorioides), cockroach (Periplaneta americana), carp (Cyprinus carpio) and tench (Tinca tinca) were studied by means of different light and electron microscopic methods. The nitroblue tetrazolium staining revealed that the myenteric plexuses of the above species are composed of nerve cells, a network of varicose nerves and nerve bundles. Instead of highly organized ganglia, single neurons or small groups of 2-4 cells are characteristic of the invertebrates and fish studied. Catecholaminergic fluorescence induced by glyoxylic acid was detected in the muscular layer of the entire alimentary tract in snail and the hindgut of tench. Fluorescent nerves and perikarya were frequent in the snail gut, while only nerves and no perikarya were found in tench. A close contact between enteric muscles and nerves is the most common form of enteric neuromuscular junction in both the smooth (i.e. the molluscan and fish gut) and the striated (i.e. the insect gut) musculature. The striated musculature (i.e. the insect gut, the oesophagus of carp, and the oesophagus, stomach and the midgut of tench) also receives a synaptic input. Cytochemical evidence is provided of the cholinergic character of fish motor endplates. The ultrastructural appearance and vesicle population of certain nerve terminals suggest a universal role of aminergic and peptidergic control in gut motility.     

Topographical relationships of intramuscular nerves and vessels of the motor endplates in the thigh and gluteal regions of human fetuses: an immunohistochemical study

Purpose

The aim of this study was to describe topography of vessels and nerves in striated muscles to understand individual muscle function.

Materials and methods

Immunohistochemistry for nerve and artery was used to examine the thigh and gluteal muscles of six human midterm fetuses.

Results

The supplying nerves often accompanied arteries along epimysium bundling muscle fibers as well as in the covering fascia surrounding the entire muscle mass. However, courses of nerve twigs were usually independent of those of vessels in muscle bundles. Notably, irrespective of whether or not the vascular bundle accompanied the nerves at the muscle surface or hilus, most of the motor endplate bands did not accompany the vessels.

Conclusion

Since the motor endplates were low vascularised, a chemical induction of vessels for nerve terminal development (or the reversed induction) seemed unlikely in striated muscles. In contrast to proprioceptive neuromuscular facilitation, manual stimulation of the endplate bands may stimulate muscle activity without sympathetic reflexes through vessel-accompanying nerves.

     

The innervation of sheep mesenteric veins

1. An isolated preparation of sheep mesenteric vein is described from which contractions of the longitudinal smooth muscle of the adventitia have been recorded in response to stimulation of intramural and periarterial nerves.2. The preparation did not respond to single stimuli but the relation between amplitude of response and frequency of stimulation was characteristic of that described for other smooth muscles innervated by sympathetic nerves.3. Responses were blocked by tetrodotoxin, guanethidine, and by a number of alpha-receptor blocking drugs. Responses to peri-arterial stimulation were unaffected by hexamethonium. It was concluded that the longitudinal smooth muscle is supplied with post-ganglionic noradrenergic motor nerves and the presence of such fibres in the adventitia was confirmed by fluorescence microscopy.4. Acetylcholine also caused contractions. Although a direct excitatory action on the smooth muscle could not be excluded, results suggest that acetylcholine may release noradrenaline from the axons of the sympathetic ground plexus.     

A REPORT ON THE PATHOLOGY OF TYPE A BOTULISM

An autopsy case of type A botulism, a sacrifice during the first outbreak in Japan, was presented. The patient exhibited typical neuromuscular symptoms and died on the 8th day from the onset of illness. Type A Clostridium botulinum was demonstrated from the stools and the toxin from the blood serum during the course of disease. The infection source of botulinus bacilli, however, was not clarified. The autopsy diagnoses were made as follows; 1) type A botulism, 2) bronchopneumonia, 3) respirator brain, 4) congestion, 5) hemorrhage in vagal nerve, myocardium and endometrium, 6) gastric erosion, 7) cloudy swelling of kidneys, 8) enterocolitis, 9) focal necrosis of liver and adrenals, 10) demyelination of cranial nerves, and 11) focal hyaline degeneration of striated and smooth muscles and myocardium. The botulinus toxin was confirmed from the samples of cardiac blood at autopsy.     

Neural control of the internal anal sphincter motility.

Control mechanism of smooth muscle movement of the internal anal sphincter (IAS) by enteric and extrinsic neuvous systems in the dog was investigated. Responses of IAS muscle strips to electrical field stimulation (EFS) and neurotransmitter agents were recorded in vitro. The contraction response to norepinephrine or to EFS was inhibited by phentolamine. The relaxation induced by EFS was not affected by phentolamine, propranolol or atropine. The mechanical activity of smooth muscle in colon and anorectum during spontaneous defecation was recorded using strain gauge force transducers. The colon and anorectum showed the characteristic motility pattern during defecation: 1) The giant migrating contraction of the colon propagated to the rectum, 2) The relaxation of the rectum prior to the contraction, and 3) The IAS muscles continued to relax while the giant contractions of the colon were migrating to the rectum. Sacral nerves were stimulated electrically and the responses of smooth muscles in the rectum and IAS were recorded. The sacral nerve stimulation induced a relaxation followed by contraction of smooth muscle in the rectum and the relaxation in IAS. The mechanical responses of smooth muscle in the IAS were modulated by alpha-adrenergic excitatory and non-adrenergic, non-cholinergic inhibitory nerves. During defecation, the relaxation of IAS smooth muscle was associated with a characteristic motility pattern of the colon and anorectum. The enteric nervous systems may be organizing the motility of these muscles by way of the motor neurones under the control the extrinsic nervous systems.     

On Structure-Function Relationships in the Female Human Urethra: A Finite Element Model Approach

Remarkably little is known about urethral striated and smooth muscle and vascular plexus contributions to maintaining continence or initiating micturition. We therefore developed a 3-D, multiphysics, finite element model, based on sequential MR images from a 23-year-old nulliparous heathy woman, to examine the effect of contracting one or more individual muscle layers on the urethral closure pressure (UCP). The lofted urethra turned out to be both curved and asymmetric. The model results led us to reject the current hypothesis that the striated and smooth muscles contribute equally to UCP. While a simulated contraction of the outer (circular) striated muscle increased closure pressure, a similar contraction of the large inner longitudinal smooth muscle both reduced closure pressure and shortened urethral length, suggesting a role in initiating micturition. When age-related atrophy of the posterior striated muscle was simulated, a reduced and asymmetric UCP distribution developed in the transverse plane. Lastly, a simple 2D axisymmetric model of the vascular plexus and lumen suggests arteriovenous pressure plays and important role in helping to maintain luminal closure in the proximal urethra and thereby functional urethral length. More work is needed to examine interindividual differences and validate such models in vivo.

     

Permeation and distribution of deuterated and triated water in smooth and striated muscle

1. The diffusion of deuterated water (HDO) into and out of isolated guinea-pig taenia coli and frog sartorius was followed by means of a recording electronic microbalance.2. A comparison was made of the rates of efflux of deuterated and tritiated (HTO) water using the microbalance and a standard tracer technique.3. The time course of the exchange of HDO in both smooth and striated muscle was fitted to the sum of two exponential functions; however, it was not possible to correlate sizes of the intra- and extracellular spaces in the muscles with the sizes of the two compartments in model systems based on compartmental theory of tracer kinetics.4. The efflux of HDO, which was measured by means of the microbalance under stagnant conditions, occurred at a rate approximately 3 times slower than the efflux of HTO which took place while muscles were agitated vigorously in their bathing media.5. There was a marked deviation at short times from a double exponential time course during the efflux of HTO.6. Values of the tracer water permeability, P(d), of smooth and striated muscle fibres, and the extracellular space, E, of the muscles were obtained using a computer to numerically evaluate the series solutions of the equations describing the permeation of labelled water in the muscles.7. It was necessary to assume a value for the diffusion coefficient of the tracer in extracellular fluid in order to compute a unique fit to an exchange curve.8. Values of P(d) and E given by the analysis depended upon the method used for monitoring the exchange, and an interpretation of this dependence was made difficult by the variation in the thickness of unstirred layers on the surface of the muscles under the different experimental conditions.