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At least 19 recordsLinked to original sources
PubMed1994

The Caenorhabditis elegans NK-2 class homeoprotein CEH-22 is involved in combinatorial activation of gene expression in pharyngeal muscle.

The pharyngeal muscles of Caenorhabditis elegans are single sarcomere muscles used for feeding. Like vertebrate cardiac and smooth muscles, C. elegans pharyngeal muscle does not express any of the known members of the MyoD family of myogenic factors. To identify mechanisms regulating gene expression in this tissue, we have characterized a pharyngeal muscle-specific enhancer from myo-2, a myosin heavy chain gene expressed exclusively in pharyngeal muscle. Assaying enhancer function in transgenic animals, we identified three subelements, designated A, B and C, that contribute to myo-2 enhancer activity. These subelements are individually inactive; however, any combination of two or more subelements forms a functional enhancer. The B and C subelements have distinct cell type specificities. A duplication of B activates transcription in a subset of pharyngeal muscles (m3, m4, m5 and m7). A duplication of C activates transcription in all pharyngeal cells, muscle and non-muscle. Thus, the activity of the myo-2 enhancer is regulated by a combination of pharyngeal muscle-type-specific and organ-specific signals. Screening a cDNA expression library, we identified a gene encoding an NK-2 class homeodomain protein, CEH-22, that specifically binds a site necessary for activity of the B subelement. CEH-22 protein is first expressed prior to myogenic differentiation and is present in the same subset of pharyngeal muscles in which B is active. Expression continues throughout embryonic and larval development. This expression pattern suggests CEH-22 plays a key role in pharyngeal muscle-specific activity of the myo-2 enhancer.

Animals↗
PubMed2001

Multiple enhancers contribute to expression of the NK-2 homeobox gene ceh-22 in C. elegans pharyngeal muscle.

Gene expression in the pharyngeal muscles of C. elegans is regulated in part by the NK-2 family homeodomain factor CEH-22, which is structurally and functionally related to Drosophila Tinman and the vertebrate Nkx2-5 factors. ceh-22 is expressed exclusively in the pharyngeal muscles and is the earliest gene known to be expressed in this tissue. Here we characterize the ceh-22 promoter region in transgenic C. elegans. A 1.9-kb fragment upstream of ceh-22 is sufficient to regulate reporter gene expression in a pattern identical to the endogenous gene. Within this promoter we identified two transcriptional enhancers and characterized their cell type and temporal specificity. The distal enhancer becomes active in the pharynx near the time that ceh-22 expression initiates; however, it becomes active more broadly later in development. The proximal enhancer becomes active after the onset of ceh-22 expression, but it is active specifically in the ceh-22-expressing pharyngeal muscles. We suggest these enhancers respond to distinct signals that initiate and maintain ceh-22 gene expression. Proximal enhancer activity requires a short segment containing a CEH-22 responsive element, suggesting that CEH-22 autoregulates its own expression.

Animals↗
PubMed1997

The Caenorhabditis elegans NK-2 homeobox gene ceh-22 activates pharyngeal muscle gene expression in combination with pha-1 and is required for normal pharyngeal development.

Pharyngeal muscle development in the nematode Caenorhabditis elegans appears to share similarities with cardiac muscle development in other species. We have previously described CEH-22, an NK-2 class homeodomain transcription factor similar to Drosophila tinman and vertebrate Nkx2-5, which is expressed exclusively in the pharyngeal muscles. In vitro, CEH-22 binds the enhancer from myo-2, a pharyngeal muscle-specific myosin heavy chain gene. In this paper, we examine the role CEH-22 plays in pharyngeal muscle development and gene activation by (a) ectopically expressing ceh-22 in transgenic C. elegans and (b) examining the phenotype of a ceh-22 loss-of-function mutant. These experiments indicate that CEH-22 is an activator of myo-2 expression and that it is required for normal pharyngeal muscle development. However, ceh-22 is necessary for neither formation of the pharyngeal muscles, nor for myo-2 expression. Our data suggest parallel and potentially compensating pathways contribute to pharyngeal muscle differentiation. We also examine the relationship between ceh-22 and the pharyngeal organ-specific differentiation gene pha-1. Mutations in ceh-22 and pha-1 have strongly synergistic effects on pharyngeal muscle gene expression; in addition, a pha-1 mutation enhances the lethal phenotype caused by a mutation in ceh-22. Wild-type pha-1 is not required for the onset of ceh-22 expression but it appears necessary for maintained expression of ceh-22.

Animals↗
PubMed1989

Continuous electromyographic recordings of pharyngeal muscle activity in normal and previously denervated muscles in dogs.

Continuous electromyographic recordings of pharyngeal muscle activity were made in 5 clinically normal control dogs and in 7 dogs 3 years after partial denervation of the pharyngeal muscles. Electromyographic recordings were made of the sequence of actions of each muscle and of the combined muscle activity, at rest and during swallowing of food. During 30-second periods, the recordings were digitalized and stored on diskette for further analysis. All control dogs had a distinct pattern of muscle activity during swallowing, the onset being in a constant order (hyopharyngeal, thyropharyngeal, and cricopharyngeal) and bilaterally synchronous. While eating, each dog had about 5 to 12 short periods of synchronous activity in each muscle, between the swallowing actions. During the resting period, there were longer periods of activity, which were synchronous with respiration. In each denervated dog, there were normal and irregular swallowing actions. Swallowing activity was recognized, but the sequence of hyopharyngeal, thyropharyngeal, and cricopharyngeal muscle activity was irregular and different from that in control dogs. Partial denervation of the pharyngeal muscles does not seriously impair motor activity of the muscles, but does alter the sequence of activity in the pharyngeal muscles during swallowing.

Animals↗
PubMed2004

Regional effects of selective pharyngeal muscle activation on airway shape.

Pharyngeal airway fiberoptic imaging was performed in 10 decerebrate cats to determine the effect of selective pharyngeal muscle activation on airway shape. At intraluminal pressures from 6 to -6 cm H2O, maximum anteroposterior and lateral diameters were measured in the rostral oropharynx, caudal oropharynx, and velopharynx with and without bilateral stimulation of the medial hypoglossus (HG), lateral HG, whole HG, glossopharyngeus, and pharyngeal branch of vagus nerves. At all three airway levels without nerve stimulation, the increase in diameter with increasing pressure was greater in the lateral than anteroposterior dimension. Stimulation of the hypoglossal and glossopharyngeus nerves caused greater increases in lateral than anteroposterior diameter in all three regions with different effects across nerves and regions. Stimulation of these four nerves frequently caused greater increases in both diameters, as the airway cross-sectional area was decreased by lowering airway pressure. Stimulation of the pharyngeal branch of vagus resulted in greater decreases in lateral than anteroposterior dimension in the caudal oropharynx and velopharynx, especially as airway cross-sectional area was increased by increasing intraluminal pressure. The results indicate that selective activation of pharyngeal muscles in cats frequently results in greater changes in lateral than anteroposterior airway diameter and that these effects are dependent on airway region and cross-sectional area.

Airway Resistance↗
PubMed2004

An early pharyngeal muscle enhancer from the Caenorhabditis elegans ceh-22 gene is targeted by the Forkhead factor PHA-4.

Caenorhabditis elegans pharyngeal muscle development involves ceh-22, an NK-2 family homeobox gene related to genes controlling heart development in other species. ceh-22 is the earliest known gene expressed in the pharyngeal muscles and is likely regulated directly by factors specifying pharyngeal muscle fate. We have previously implicated the ceh-22 distal enhancer in initiating ceh-22 expression. Here we analyze the distal enhancer using functional and comparative assays. The distal enhancer contains three subelements contributing additively to its activity, and functionally important regulatory sequences are highly conserved in Caenorhabditis briggsae. One subelement, termed DE3, is strongly active in the pharyngeal muscles, and we identified two short oligonucleotides (de199 and de209) contributing to DE3 activity. Multimerized de209 enhances transcription similarly to DE3 specifically in the pharyngeal muscles, suggesting it may be an essential site regulating ceh-22. de209 binds the pan-pharyngeal Forkhead factor PHA-4 in vitro and responds to ectopic pha-4 expression in vivo, suggesting that PHA-4 directly initiates ceh-22 expression through de209. Because de209 enhancer activity is primarily limited to the pharyngeal muscles, we hypothesize that de209 also binds factors functioning with PHA-4 to specifically activate ceh-22 expression in pharyngeal muscle.

Animals↗
PubMed1963

OBSERVATIONS ON THE FINE STRUCTURE OF PHARYNGEAL MUSCLE IN THE PLANARIAN DUGESIA TIGRINA.

Pharyngeal muscle of the planarian Dugesia tigrina was studied by electron microscopy after osmium tetroxide fixation. The muscle cell was observed to contain one myofibril or bundle of myofilaments parallel to its longitudinal axis. The myofilaments were of two types, different in size and distribution. No Z lines or myofilament organization into cross or helical striations were seen. Dense bodies were seen as projections from an invagination of the plasma membrane and as dense lines parallel to the myofilaments. The muscle cells are surrounded by a plasma membrane which is structurally associated with dense body projections, with vesicles and cisternae of sarcoplasmic reticulum, and with synaptic nerve endings. The cell has sarcoplasmic projections perpendicular to its long axis; these projections are seen to contain the nucleus or mitochondria and granules. Mitochondria and granules are also seen in a sarcoplasm rim around the fibril. The dense bodies may serve as attachment for thin myofilaments and function in transmission of stimuli from plasma membrane to the interior of the fibril.

Animals↗
PubMedDate not supplied

[Respiratory function of pharyngeal muscles].

This article reviews experimental studies of pharyngeal muscles with emphasis on m. genioglossus as a major muscle dilating pharynx and discusses neuromuscular mechanisms that maintains patency of upper airway. Mechanisms of inspiratory activation of genioglossus muscle in comparative with diaphragm are also discussed. Experimental data suggesting that upper airway muscles have a significant role in compensation of added inspiratory load are presented. It allows to regard pharyngeal dilating muscles as accessory muscles of respiration. Activation of m. genioglossus (together with others muscles dilating the pharynx) decreases airway resistance and thereby facilitates the load compensation function of "pumping" muscles. Similar to diaphragm involvement of the pharynx dilating muscles in the load compensatory response is resulted from a complex integration of several influences originating from mechano- and chemoreceptors.

Animals↗
PubMed2006

The T-box factor TBX-2 and the SUMO conjugating enzyme UBC-9 are required for ABa-derived pharyngeal muscle in C. elegans.

The C. elegans pharynx is produced from the embryonic blastomeres ABa and MS. Pharyngeal fate in the ABa lineage is specified by the combined activities of GLP-1/Notch-mediated signals and the TBX-37 and TBX-38 T-box transcription factors. Here, we show another T-box factor TBX-2 also functions in ABa-derived pharyngeal development. tbx-2 mutants arrest as L1 larvae lacking most or all ABa-derived pharyngeal muscles. In comparison, tbx-2 mutants retain ABa-derived marginal cells and pharyngeal muscles derived from MS. A tbx-2Colon, two colonsgfp translational fusion is expressed in a dynamic pattern in C. elegans embryos beginning near the 100-cell stage. Early expression is limited to a small number of cells, which likely include the ABa-derived pharyngeal precursors, while later expression is observed in body wall muscles and a subset of pharyngeal neurons. TBX-2 contains 2 consensus sumoylation sites, and it interacts in a yeast two-hybrid assay with the UBC-9 and GEI-17 components of the C. elegans SUMO-conjugating pathway. ubc-9(RNAi) has been previously shown to cause variable embryonic and larval arrest, and we find that, like tbx-2 mutants, ubc-9(RNAi) animals lack ABa-derived pharyngeal muscles. ubc-9(RNAi) also alters the subnuclear distribution of TBX-2::GFP fusion protein, suggesting that UBC-9 and TBX-2 interact in C. elegans. Together, these results indicate that TBX-2 and SUMO-conjugating enzymes are necessary for ABa-derived pharyngeal muscle, and we hypothesize that TBX-2 function requires sumoylation. Sumoylation is increasingly recognized as an important mechanism controlling activity of many nuclear factors, and these results provide the first evidence that T-box factor activity may require sumoylation.

Animals↗
PubMed2001

Effects of pharyngeal muscle activation on airway size and configuration.

Fiberoptic imaging was performed in six decerebrate, tracheotomized cats to determine the effect of pharyngeal muscle activation on the pharyngeal airway. The fiberoptic scope was advanced through the rostral trachea into the pharynx. Computer-based planimetry was used to measure airway area and maximum anteroposterior and lateral diameters in the rostral oropharynx, velopharynx, and caudal oropharynx. Cuff electrodes stimulated the bilateral distal cut ends of the following nerves: medial hypoglossus (MHG), lateral hypoglossus (LHG), glossopharyngeus, and pharyngeal branch of vagus (PBV). The velopharyngeal area increased with stimulation of the MHG, MHG plus LHG, and glossopharyngeus. The velopharyngeal area decreased with PBV stimulation. Similar effects occurred in the caudal oropharynx. The percent increase in velopharyngeal area with combined MHG and LHG stimulation was greater than the sum of the increases stimulating either branch alone. In the rostral oropharynx, airway area increased with individual and combined stimulation of the MHG and LHG. Changes in airway area at the different levels were concentric with the HG stimulations, but glossopharyngeal stimulation resulted in a greater increase in lateral than anteroposterior wall movement. The results indicate that the mechanical effects of pharyngeal muscle contraction depend on the airway level and the specific muscles that are activated.

Animals↗
PubMed2004

Slow Ca2+ dynamics in pharyngeal muscles in Caenorhabditis elegans during fast pumping.

The pharyngeal muscles of Caenorhabditis elegans are composed of the corpus, isthmus and terminal bulb from anterior to posterior. These components are excited in a coordinated fashion to facilitate proper feeding through pumping and peristalsis. We analysed the spatiotemporal pattern of intracellular calcium dynamics in the pharyngeal muscles during feeding. We used a new ratiometric fluorescent calcium indicator and a new optical system that allows simultaneous illumination and detection at any two wavelengths. Pumping was observed with fast, repetitive and synchronous spikes in calcium concentrations in the corpus and terminal bulb, indicative of electrical coupling throughout the muscles. The posterior isthmus, however, responded to only one out of several pumping spikes to produce broad calcium transients, leading to peristalsis, the slow and gradual motion needed for efficient swallows. The excitation-calcium coupling may be uniquely modulated in this region at the level of calcium channels on the plasma membrane.

Animals↗
PubMed1990

Manometry and electromyography of the pharyngeal muscles in patients with dysphagia.

Simultaneous recording of the electromyographic activity of the pharyngeal muscles and the intraluminal pressure in the upper sphincter zone was performed routinely in patients with swallowing problems for the first time, to our knowledge. This technique was found to be very useful for the localization of the "site of lesion." The procedure is safe, easy to master, and causes minimal inconvenience. It can reveal, in the most direct way, whether the disturbance is in the hypopharyngeal musculature (represented by the inferior constrictor muscle), in the cricopharyngeal muscle (spasm or lack of relaxation), or in the synchronization between them. Simultaneous recording of intraluminal pressure adds valuable information about the mechanical events associated with electromyographic activity. It was found that in pathologic cases there is quite often no correlation between the electrical and mechanical events. Thus, simultaneous recording of both electrical and mechanical events is essential for the understanding of the pathophysiology of disturbances of deglutition.

Adult↗
PubMed2005

Actions of glutamate and ivermectin on the pharyngeal muscle of Ascaridia galli: a comparative study with Caenorhabditis elegans.

The actions of glutamate and ivermectin were examined in the pharynx of Ascaridia galli and the results compared with those on the pharynx of Caenorhabditis elegans. In both preparations glutamate elicits a depolarization and inhibition of pharyngeal pumping, but the response of the pharynx of A. galli was much less than for C. elegans. This may be either because the pharyngeal membrane potential of the former is closely linked to the equilibrium potential for chloride ions (E(Cl)) while that of C. elegans is independent of E(Cl), or that there is a lower density of glutamate receptors on the pharyngeal muscle of A. galli compared with C. elegans. The maximum depolarization to glutamate of the pharyngeal muscle was 4.5+/-0.8 mV in A. galli while it was >25 mV in C. elegans. Picrotoxin was a weak antagonist of the glutamate response in both species. Flufenamic acid, pentobarbitone and flurazepam had no significant effect on either preparation at concentrations up to 100 microM. Three glutamate receptor agonists, ibotenate, kainate and quisqualate were all more potent than glutamate on the A. galli pharyngeal muscle. In contrast, only ibotenate was more potent than glutamate in C. elegans pharynx, the other two agonists being approximately 20 times less potent. The potency of ivermectin differed markedly between the two species, being approximately three orders of magnitude less potent on the pharynx of A. galli compared with C. elegans. This study demonstrates clear differences between the properties of the pharyngeal muscle of the two species and shows that care must be taken when extrapolating data from free-living to parasitic species of nematode.

Action Potentials↗
PubMed1995

The action of serotonin and the nematode neuropeptide KSAYMRFamide on the pharyngeal muscle of the parasitic nematode, Ascaris suum.

The pharyngeal component of the enteric nervous system of the parasitic nematode, Ascaris suum exhibits immunoreactivity for serotonin (5-hydroxytryptamine or 5-HT) and for FMRFamide-like peptides. This paper describes the application of an in vitro pharmacological approach to investigate the functional role of 5-HT and FMRFamide-like peptides. The pharyngeal pumping behaviour of Ascaris suum was monitored using a modified pressure transducer system which measures pharyngeal pressure changes and therefore pumping. The pharynx did not contract spontaneously; however, 5-HT (10-1000 microM) stimulated pumping at a frequency of 0.5 Hz. FMRFamide had no apparent effect on pharyngeal pumping. The native nematode FMRFamide-related peptide (FaRP), KSAYMRFamide inhibited the pumping elicited by 5-HT. The duration of inhibition was dose-dependent (0.1-1000 nM) with a threshold of 0.1 nM. In 4 preparations, the inhibition of the pharyngeal muscle was preceded by an initial excitation and increase in the amplitude of pharyngeal pressure changes. The pharynx is involved in various nematode processes, including feeding, regulation of hydrostatic pressure and excretion. The role of 5-HT and KSAYMRFamide in the pharyngeal function of nematodes is discussed.

Amino Acid Sequence↗
PubMed1986

The origins of innervation of the canine caudal pharyngeal muscles: an HRP study.

In deglutition, movements of the tongue and oropharynx direct a bolus to the laryngopharynx. The major muscles of this region, which includes the 'cricopharyngeal sphincter', must undergo sequential relaxation and contraction for correct swallowing action. The innervation of the caudal pharyngeal muscles involved in this action in the dog have not been determined previously by sensitive neuroanatomical techniques. In this study, the location of efferent and afferent neurons innervating the left cricopharyngeus, thyropharyngeus and hyopharyngeus muscles was determined by horseradish peroxidase (HRP) histochemistry in 7 puppies. Labeled cells were found ipsilaterally in the supraspinal nucleus, nucleus ambiguus (including nucleus retrofacialis) and nucleus intercalatus of all animals, in the parasympathetic nucleus of X (dorsal vagal efferent nucleus) of 6 animals, and in the hypoglossal nucleus of 4 animals. Small numbers of HRP-labeled cells were found contralaterally in the supraspinal nucleus of all animals, and in the rostral nucleus ambiguus, in the nucleus intercalatus and the parasympathetic nucleus of X of fewer animals. This defines a more extensive source of efferent neurons for these muscles than had been reported for the cat. Labeled postganglionic sympathetic neurons were found bilaterally in the cranial (superior) cervical, middle cervical and cervicothoracic (stellate) ganglia. Labeled afferent neurons were seen bilaterally in the proximal vagal (jugular) and distal vagal (nodose) ganglia and in the C1-C4 spinal ganglia. The location of sympathetic and sensory nerve cell bodies of the muscles of the laryngopharynx has not been previously reported.

Animals↗
PubMed2001

Negative pressure effects on mechanically opposing pharyngeal muscles in awake and sleeping goats.

Our aim was to investigate the effects of the negative pressure reflex on mechanically opposing pharyngeal muscles during wakefulness, slow-wave sleep (SWS), and rapid eye movement (REM) sleep. In four goats with isolated upper airways, we measured tracheal airflow and electrical activity of the thyropharyngeus (TP; constricting), the stylopharyngeus (SP; dilating), and the diaphragm (Dia). In the wakefulness state in response to negative pressure tests, TP decreased (65%), SP increased (198%), and tidal volume (VT) (66%) and rate of rise of Dia (Dia(slope), 69%) decreased (P < 0.02). Similarly, during SWS, the negative pressure response of TP (31%), VT (61%), and Dia(slope) (60%) decreased, whereas SP (113%) increased, relative to SWS control (P < 0.02). In REM sleep, the negative pressure response by TP and SP were small, whereas both VT (38%) and Dia(slope) (24%) were greatly decreased (P < 0.02) compared with REM control. Inspiratory duration remained unchanged in response to negative pressure tests in all states. These data provide evidence that mechanically opposing inspiratory and expiratory pharyngeal muscles are reciprocally controlled and their response to negative pressure are state dependent.

Anesthesia↗
PubMedDate not supplied

[Physiology of pharyngeal muscles after surgical restoration of the velopharyngeal sphincter].

INTRODUCTION: Speech velopharyngeal sphincter restoration is generally performed by pharyngeal flap or sphincter pharyngoplasty. OBJECTIVE: Evaluate pharyngeal muscle physiology after pharyngeal flap or sphincter pharyngoplasty using simultaneous electromyography and videonasopharyngoscopy. MATERIAL AND METHODS: Forty patients were studied. Twenty patients were operated on with an upper base pharyngeal flap. Twenty patients were operated on with sphincter pharyngoplasty. The following muscles were studied: superior constrictor pharyngeus, palatopharyngeus, and levator veli palatini. RESULTS: None of the patients studied showed electromyographic activity in the lateral flaps of tile pharyngoplasties. None showed electromyographic activity of the upper base pharyngeal flaps. All patients demonstrated strong electromyographic activity on the superior constrictor pharyngeus and the levator veli palatini. CONCLUSIONS: Lateral pharyngeal flaps in cases of sphincter pharyngoplasties and the central pharyngeal flap in cases of pharyngeal flaps, do not create new sphincters for velopharyngeal closure. The participation of these structures is passive, increasing tissue volume in specific areas, whereas their movements are caused by the contraction of the superior constrictor pharyngeus and the levator veli palatini.

Adolescent↗