Relationship between esophageal muscle thickness and intraluminal pressure: an ultrasonographic study

A number of studies show a close temporal relationship between the rate of change in muscle thickness as detected by high-frequency intraluminal ultrasonography (HFIUS) and intraluminal pressure measured by manometry. There is a marked variability in esophageal contraction amplitude from one swallow to another at a given level in the esophagus and along the length of the esophagus. Furthermore, peristaltic pressures are higher in the distal compared with the proximal esophagus. The goal of this study was to evaluate the relationship between the baseline and peak muscle thickness and the contraction amplitude during swallow-induced contractions along the length of the esophagus. Fifteen normal subjects were studied using simultaneous esophageal pressures and HFIUS or HFIUS alone. Recordings were made during baseline and standardized swallows in the lower esophageal sphincter (LES) and at 2, 4, 6, 8, and 10 cm above the LES. HFIUS images were digitized, and esophageal muscle thickness and peak contraction amplitudes were measured. In the resting state, muscle thickness is higher in the LES compared with the rest of the esophagus. Baseline muscle thickness is also significantly higher at 2 cm vs. 10 cm above the LES. In a given subject and among different subjects, there is a good relationship between peak muscle thickness and peak peristaltic pressures (r = 0.55) at all sites along the length of the esophagus. The positive correlation between pressure and muscle thickness implies that the mean circumferential wall stress is fairly uniform from one swallow to another, irrespective of the contraction amplitude.     

Mechanics and hemodynamics of esophageal varices during peristaltic contraction

Our hypothesis states that variceal pressure and wall tension increase dramatically during esophageal peristaltic contractions. This increase in pressure and wall tension is a natural consequence of the anatomy and physiology of the esophagus and of the esophageal venous plexus. The purpose of this study was to evaluate variceal hemodynamics during peristaltic contraction. A simultaneous ultrasound probe and manometry catheter was placed in the distal esophagus in nine patients with esophageal varices. Simultaneous esophageal luminal pressure and ultrasound images of varices were recorded during peristaltic contraction. Maximum variceal cross-sectional area and esophageal luminal pressures at which the varix flattened, closed, and opened were measured. The esophageal lumen pressure equals the intravariceal pressure at variceal flattening due to force balance laws. The mean flattening pressures (40.11 +/- 16.77 mmHg) were significantly higher than the mean opening pressures (11.56 +/- 25.56 mmHg) (P < or = 0.0001). Flattening pressures >80 mmHg were generated during peristaltic contractions in 15.5% of the swallows. Variceal cross-sectional area increased a mean of 41% above baseline (range 7-89%, P < 0.0001) during swallowing. The peak closing pressures in patients that experience future variceal bleeding were significantly higher than the peak closing pressures in patients that did not experience variceal bleeding (P < 0.04). Patients with a mean peak closing pressure >61 mmHg were more likely to bleed. In this study, accuracy of predicting future variceal bleeding, based on these criteria, was 100%. Variceal models were developed, and it was demonstrated that during peristaltic contraction there was a significant increase in intravariceal pressure over baseline intravariceal pressure and that the peak intravariceal pressures were directly proportional to the resistance at the gastroesophageal junction. In conclusion, esophageal peristalsis in combination with high resistance to blood flow through the gastroesophageal junction leads to distension of the esophageal varices and an increase in intravariceal pressure and wall tension.     

Cholinergic stimulation induces asynchrony between the circular and longitudinal muscle contraction during esophageal peristalsis

In healthy subjects, a close temporal correlation exists between contractions of the circular muscle (CM) and longitudinal muscle (LM) layers of the esophagus. Patients with nutcracker esophagus show disassociation between the peak of contractions of the CM and LM layers and the peak of contraction 1-3 s apart (Jung HY, Puckett JL, Bhalla V, Rojas-Feria M, Bhargava V, Liu J, Mittal RK. Gastroenterology 128: 1179-1186, 2005). The purpose of the present study was to evaluate the effect of acetylcholinesterase inhibitor (edrophonium) and acetylcholine receptor antagonist (atropine) on human esophageal peristalsis in normal subjects. High-frequency intraluminal ultrasound imaging and manometry were performed simultaneously during swallow-induced peristalsis in ten normal subjects. Standardized 5-ml water swallows were recorded 2 cm above the lower esophageal sphincter under three study conditions: control, edrophonium (80 microg/kg iv), and atropine (10 microg/kg iv). A close temporal correlation exists between the peak pressure and peak wall thickness during the control period. The mean time lag between the peak LM and peak CM contraction was 0.03 s. After edrophonium administration, the mean contraction amplitude increased from 101 +/- 9 mmHg to 150 +/- 20 mmHg (P < 0.05) and mean peak muscle thickness increased from 3.0 +/- 0.2 mm to 3.6 +/- 0.3 mm (P < 0.01), and duration of both CM and LM contractions were also increased. Furthermore, the mean time difference between the peak LM and CM was increased to 1.1 s, (ranging 0.2 to 3.4 s) (P < 0.0001). We conclude that cholinomimetic agent induces discoordination between the two muscle layers of the esophagus.     

A novel pattern of longitudinal muscle contraction with subthreshold pharyngeal stimulus: a possible mechanism of lower esophageal sphincter relaxation

A subthreshold pharyngeal stimulus induces lower esophageal sphincter (LES) relaxation and inhibits progression of ongoing peristaltic contraction in the esophagus. Recent studies show that longitudinal muscle contraction of the esophagus may play a role in LES relaxation. Our goal was to determine whether a subthreshold pharyngeal stimulus induces contraction of the longitudinal muscle of the esophagus and to determine the nature of this contraction. Studies were conducted in 16 healthy subjects. High resolution manometry (HRM) recorded pressures, and high frequency intraluminal ultrasound (HFIUS) images recorded longitudinal muscle contraction at various locations in the esophagus. Subthreshold pharyngeal stimulation was induced by injection of minute amounts of water in the pharynx. A subthreshold pharyngeal stimulus induced strong contraction and caudal descent of the upper esophageal sphincter (UES) along with relaxation of the LES. HFIUS identified longitudinal muscle contraction of the proximal (3-5 cm below the UES) but not the distal esophagus. Pharyngeal stimulus, following a dry swallow, blocked the progression of dry swallow-induced peristalsis; this was also associated with UES contraction and descent along with the contraction of longitudinal muscle of the proximal esophagus. We identify a unique pattern of longitudinal muscle contraction of the proximal esophagus in response to subthreshold pharyngeal stimulus, which we propose may be responsible for relaxation of the distal esophagus and LES through the stretch sensitive activation of myenteric inhibitory motor neurons.     

Synchrony between circular and longitudinal muscle contractions during peristalsis in normal subjects

The current understanding is that longitudinal muscle contraction begins before and outlasts circular muscle contraction during esophageal peristalsis in normal subjects. The goal of our study was to reassess the relationship between the contractility of two muscle layers using novel ways to look at the muscle contraction. We studied normal subjects using synchronized high-frequency ultrasound imaging and manometry. Swallow-induced peristalsis was recorded at 5 and 10 cm above the lower esophageal sphincter (LES). Ultrasound (US) images were analyzed for muscle cross-sectional area (CSA) and circularity index of the esophagus during various phases of esophageal contraction. A plot of the M mode US image, muscle CSA, and esophageal circularity index was developed to assess the temporal correlation between various parameters. The muscle CSA wave began before and lasted longer than the contraction pressure wave at both 5 and 10 cm above the LES. M mode US images revealed that the onset of muscle CSA wave was temporally aligned with the onset of lumen collapse. The peak muscle CSA occurred in close proximity with the peak pressure wave. The esophagus started to become more circular (decrease in circularity index) with the onset of the muscle CSA wave. The circularity index and muscle CSA returned to the baseline at approximately the same time. In conclusion, the onset of lumen collapse and return of circularity index of the esophagus are likely to be the true markers of the onset and end of circular muscle contraction. Circular and longitudinal muscle layers of the esophagus contract in a precise synchronous fashion during peristalsis in normal subjects.     

Esophageal wall blood perfusion during contraction and transient lower esophageal sphincter relaxation in humans

We recently reported that esophageal contraction reduces esophageal wall perfusion in an animal study. Our aim was to determine esophageal wall blood perfusion (EWBP) during esophageal contraction and transient lower esophageal sphincter relaxations (TLESRs) in humans. We studied 12 healthy volunteers. A custom-designed laser Doppler probe was anchored to the esophageal wall, 4-6 cm above the LES, by use of the Bravo pH system so that the laser light beam stay directed toward the esophageal mucosa. A high-resolution manometry equipped with impedance electrodes recorded esophageal pressures and reflux events. Synchronized pressure, impedance, pH, and EWBP recordings were obtained during dry and wet swallows and following a meal. Stable recordings of laser Doppler EWBP were only recorded when the laser Doppler probe was firmly anchored to the esophageal wall. Esophageal contractions induced by dry and wet swallows resulted in 46 ± 9% and 60 ± 10% reduction in the EWBP, respectively (compared to baseline). Reduction in EWBP was directly related to the amplitude (curvilinear fit) and duration of esophageal contraction. Atropine reduced the esophageal contraction amplitude and decreased the EWBP reduction associated with esophageal contraction. TLESRs were also associated with reduction in the EWBP, albeit of smaller amplitude (29 ± 3%) but longer duration (19 ± 2 s) compared with swallow-induced esophageal contractions. We report 1) an innovative technique to record EWBP for extended time periods in humans and 2) contraction of circular and longitudinal muscle during peristalsis and selective longitudinal muscle contraction during TLESR causes reduction in the EWBP; 3) using our innovative technique, future studies may determine whether esophageal wall ischemia is the cause of esophageal pain/heartburn.     

Deglutitive inhibition affects both esophageal peristaltic amplitude and shortening

Deglutitive inhibition attenuates ongoing esophageal contractions if swallows are separated by short time intervals. This study aimed to determine whether esophageal shortening, mediated by longitudinal muscle, was similarly affected. Eight healthy subjects with two distal esophageal segments demarcated by mucosal clips and manometric recording sites positioned within those segments underwent concurrent manometry and fluoroscopy. Peristaltic amplitude and change in distal segment lengths were quantified during single swallows, paired swallows separated by progressively prolonged intervals, and a series of rapid repetitive swallows. During grouped swallows, deglutitive inhibition with complete attenuation of both the manometric contraction and segment shortening was evident with short-interval swallows and rapid-sequence swallows. No inhibition of either was evident with long-interval pairs. With intermediate interswallow intervals, the occurrence and degree of deglutitive inhibition between peristaltic amplitude and segment shortening were closely correlated. Deglutitive inhibition affects both the longitudinal and circular muscle layers of the esophageal wall, and the occurrence of inhibition evident in one layer is strongly correlated with the other.     

Vasoactive intestinal peptide causes peristaltic contractions in the esophageal body

Vasoactive intestinal peptide (VIP) caused a dose-dependent fall in lower esophageal sphincter (LES) pressure and dose-dependent contractions in the body of the esophagus. The response to VIP in the esophagus or LES was not modified by atropine, phentolamine, haloperidol, pyrilamine, methysergide, indomethacin and tetrodotoxin, showing that it exerts direct action at the esophageal smooth muscle. These studies suggest that VIP causes contraction in the esophageal body and relaxation of the LES by a direct action on the smooth muscle. It is possible that VIP may be the common mediator of noncholinergic, nonadrenergic neurons that cause relaxation of the lower esophageal sphincter and contraction in the esophageal body.     

Symptom hypersensitivity to acid infusion is associated with hypersensitivity of esophageal contractility

Several investigators have observed that repeated acid infusions induce stronger symptoms (symptom hypersensitivity). The goal of our study was to determine whether symptom hypersensitivity is associated with esophageal contractile hypersensitivity. Subjects with chronic heartburn symptoms underwent simultaneous pressure and ultrasound imaging of esophagus. Normal saline and 0.1 N HCl were sequentially infused into the esophagus, and subjects scored heartburn symptoms on a 1-10 scale. Saline and HCl infusions were repeated in 10 subjects with a positive Bernstein test. Esophageal contraction amplitude and duration and muscularis propria thickness were measured using a computerized method during recording. Acid infusion induced heartburn. Esophageal contractions had higher amplitudes (pressure 114.2 +/- 7.0%) and longer duration (116.8 +/- 4.4%) during acid infusion compared with saline infusion. Average muscle thickness was greater during acid infusion than saline infusion (107.0 +/- 2.0%). Sustained esophageal contractions (SECs) were identified during acid infusion. A second acid infusion (acid-2) induced heartburn with shorter latency (93.0 +/- 15.0 vs. 317.0 +/- 43.0 s) and stronger severity (8.5 +/- 0.5 vs. 5.3 +/- 0.8) than the first acid infusion (acid-1). Contraction amplitudes (140.2 +/- 13.0%), average muscle thickness (118.0 +/- 3.3%), and contraction duration (148.5 +/- 5.6 vs. 116.8 +/- 4.4%) were higher during acid-2 than acid-1. Also, numbers of SECs were greater during acid-2 than acid-1 (31 in 8 subjects vs. 11 in 6 subjects). Our data show that acid infusion into esophagus induces esophageal hypersensitivity and that a close temporal correlation exists between symptom hypersensitivity and contractility hypersensitivity.     

Effect of esophageal contraction on esophageal wall blood perfusion

Myocardial blood flow occurs during the diastolic phase of the cardiac cycle, because myocardial contraction during the systolic phase impedes myocardial perfusion. Using laser Doppler perfusion technique, we studied the effect of esophageal contraction on the esophageal wall perfusion. Studies were conducted in rats. A laser Doppler probe was anchored to the esophageal wall, and wall perfusion was studied under various experimental conditions. Increase and decrease in the systemic blood pressure induced by different pharmacological agents was associated with the increase and decrease in the esophageal wall perfusion, respectively. Esophageal contractions induced by electrical stimulation of the vagus nerve and electrical stimulation of the muscle directly resulted in a reduction in the esophageal wall perfusion, in a dose-dependent fashion. Esophageal wall perfusion could be monitored by placing the Doppler probe on the esophageal mucosa or on the outside of the esophageal wall. Esophageal contraction impedes entry of blood into the esophageal wall. Future studies may investigate if ischemia of the esophageal wall induced by sustained esophageal contractions/esophageal spasm is the cause of esophageal pain symptoms in humans.     

Esophagitis-related esophageal shortening in opossum is associated with longitudinal muscle hyperresponsiveness

Acute intraluminal acid perfusion induces esophageal shortening in humans and opossums. Lower esophageal sphincter (LES) hypotension and peristaltic dysfunction occur in patients and animal models of reflux esophagitis. This study examined whether similar shortening and motor dysfunction occur in anesthetized opossums after repeated esophageal acid exposure and whether this is associated with longitudinal muscle (LM) hyperresponsiveness. Manometry used before and after 3 consecutive days of 45-min perfusion with 100 mmol/l HCl or normal saline measured esophageal length and motor responses to induced swallows. LM electrical and mechanical responses were assessed using standard isometric tension and intracellular recording techniques. Compared with controls, repeated acid perfusion induced erosive esophagitis and significant esophageal shortening, associated with enhanced LM responses to carbachol, a significantly depolarized resting membrane potential, and abnormal spike patterns. LES resting pressure and swallow-induced peristalsis were unaffected. In this model of reflux esophagitis, marked persistent esophageal shortening and associated LM hyperresponsiveness occur before significant LES or peristaltic dysfunction, suggesting that esophageal shortening is the earliest motor disorder induced by acid injury.     

Effect of galanin and galanin antagonists on peristalsis in esophageal smooth muscle in the opossum

Galanin, a neuropeptide that is widely distributed in the esophageal nerves, is known to exert a neuromodulatory action in the gut. These studies examined the effect of galanin and galanin antagonists on esophageal peristalsis in anesthetized opossums in vivo. Intraluminal esophageal pressures were recorded at 1, 3, 5, 7, and 9 cm above the lower esophageal sphincter. Esophageal peristaltic contractions were induced by swallow and short- (1-s) and long-train (10-s) vagal stimulation (VS). Galanin (1 nmol/kg) inhibited the amplitude of swallow-induced peristaltic contractions and increased peristaltic velocity by enlarging the latency periods in the upper part of the esophagus and reducing them in the lower part. Galinin nearly abolished esophageal contractions caused by short-train VS at 5 Hz and inhibited the contractions at 10 Hz. Galanin increased latency periods induced by short-train VS with little change in the velocity of peristalsis and reduced the amplitude of both A (cholinergic) and B (noncholinergic) contractions due to long-train VS. However, the decrease in amplitude of B contractions was more marked. Galantide (3 nmol/kg) antagonized the inhibitory action of exogenous galanin on esophageal contractions elicited by short-train VS, but by itself galantide had no significant effect on esophageal contractions. In conclusion, exogenous galanin inhibits the amplitude of swallow-induced peristaltic contractions and converts them into nonperistaltic contractions by inhibiting both the cholinergic and noncholinergic components.     

Effects of cholinergic stimulation on human esophageal peristalsis.

The effects of cholinergic stimulation on esophageal peristalsis were studied in normal subjects. An intraesophageal transducer assembly was used to measure the dynamics of esophageal peristalsis before and after edrophonium chloride, 80 mug/kg intravenously. Following endrophonium, there was a marked increase in amplitude of esophageal persistalsis associated with a significant reduction in velocity of esophageal peristalsis and a significant increase in width and time of appearance of the contraction wave following a swallow. Graded doses of endrophonium all resulted in significant increases in peristaltic amplitude with the maximal response occurring at doses of 80 and 160 mug/kg. Similar results were obtained with a more direct-acting cholinergic agent, bethanechol, 80 mug/kg subcutaneously. The relevance of these results as an indication of the importance of cholinergic innervation in regulating esophageal motility are discussed.     

The mechanical advantage of local longitudinal shortening on peristaltic transport

Whereas bolus transport along the esophagus results from peristaltic contractions of the circular muscle layer, it has been suggested that local shortening of the longitudinal muscle layer concentrates circular muscle fibers in the region where the highest contractile pressures are required. Here we analyze the mechanical consequences of local longitudinal shortening (LLS) through a mathematical model based on lubrication theory. We find that local pressure and shear stress in the contraction zone are greatly reduced by the existence of LLS. In consequence, peak contractile pressure is reduced by nearly 2/3 at physiological LLS, and this reduction is greatest when peak in LLS is well aligned with peak contractile pressure. We conclude that a peristaltic wave of local longitudinal muscle contraction coordinated with the circular muscle contraction wave has both a great physiological advantage (concentrating circular muscle fibers), and a great mechanical advantage (reducing the level of contractile force required to transport the bolus), which combine to greatly reduce circular muscle tone during esophageal peristalsis.     

Effect of dry swallows and wet swallows of different volumes on esophageal peristalsis.

The effect of dry swallows and wet swallows of various volumes on esophageal function was studied in normal subjects. An intraesophageal transducer assembly was used to measure the dynamics of esophageal peristalsis. The strength of esophageal contraction (amplitude) following a 1-ml liquid bolus was similar to that following a dry swallow but was significantly less than that following a wet swallow of a larger volume. There was no difference in strength of esophageal squeeze following swallows ranging from 2 to 20 ml. In addition, a wet swallow was associated with slower wave speed, greater duration of the contraction wave, and later time of appearance of the peristaltic wave in the distal esophagus than a dry swallow. Futhermore, the incidence of peristalsis was greater with a wet swallow than a dry swallow. The results of our studies indicate that although the act of swallowing alone in man initiates peristalsis, afferent information contributes to the regulation of primary peristalsis.     

Axial stretch: A novel mechanism of the lower esophageal sphincter relaxation

Swallow and esophageal distension-induced relaxations of the lower esophageal sphincter (LES) are associated with an orad movement of the LES because of a concurrent esophageal longitudinal muscle contraction. We hypothesized that the esophageal longitudinal muscle contraction induces a cranially directed mechanical stretch on the LES and therefore studied the effects of a mechanical stretch on the LES pressure. In adult opossums, a silicon tube was placed via mouth into the esophagus and laparotomy was performed. Two needles with silk sutures were passed, 90 degrees apart, through the esophageal walls and silicon tube, 2 cm above the LES. The tube was withdrawn, and one end of each of the four sutures was anchored to the esophageal wall and the other end exited through the mouth to exert graded cranially directed stretch on the LES by using pulley and weights. A cranially directed stretch caused LES relaxation, and with the cessation of stretch there was recovery of the LES pressure. The degree an d duration of LES relaxation increased with the weight and the duration of stretch, respectively. The mean LES relaxation in all animals was 77.7 +/- 4.7%. The required weight to induce maximal LES relaxation differed in animals (714 +/- 348 g). N(G)-nitro-L-arginine, a nitric oxide inhibitor, blocked the axial stretch-induced LES relaxation almost completely (from 78 to 19%). Our data support the presence of an axial stretch-activated inhibitory mechanism in the LES. The role of axial stretch in the LES relaxation induced by swallow and esophageal distension requires further investigation.     

Sustained esophageal contraction: a motor correlate of heartburn symptom

Heartburn occurs in the presence as well as the absence of acid reflux. We searched for a motor correlate of heartburn. Twelve subjects with heartburn were studied with 24-h synchronized pressure, pH, and high-frequency intraluminal ultrasound (HFIUS) imaging of the esophagus. The HFIUS images were analyzed every 2 s for a period of 2 min before and 30 s after the onset of heartburn during 20 acid reflux-positive and 20 acid reflux-negative heartburn episodes. The esophageal muscle thickness was measured as a marker of contraction. Esophageal pressure and HFIUS images were recorded during the Bernstein test in 15 subjects. Sustained esophageal contractions (SECs) were identified during 13 of 20 heartburn episodes associated with acid reflux and 15 of 20 heartburn episodes without acid reflux. SECs were detected during 2 of 40 matched control periods only (P < 0.05). The duration of SECs was 44.9 +/- 26.9 s. The Bernstein test reproduced heartburn symptoms in 8 of 15 subjects. SECs were identified during 6 of 8 (75%) Bernstein-positive and in 1 of 7 (14.3%) Bernstein-negative tests (P = 0.04). We conclude that a SEC precedes both spontaneous and induced heartburn symptoms and may be the cause of heartburn sensation.     

Common cavity pressure during gastroesophageal reflux: reassessment using simultaneous pressure, impedance, and ultrasound imaging

An increase in intraesophageal pressure during transient lower esophageal sphincter (LES) relaxation [referred to as common cavity (CC) pressure] is thought to be a marker of gastroesophageal reflux (GER). Multiluminal impedance (MII) measurement is a sensitive marker of reflux entry into the esophagus during GER. We recorded GER using esophageal pressure, pH, impedance, and intraluminal ultrasound (US) images to understand the genesis of the esophageal CC pressure. Nine normal subjects underwent simultaneous MII/pH/pressure and US image recording of the esophagus for 2 h following a standardized meal. MII and pressure transducers were located at 5 and 15 cm above the LES. The US transducer and pH sensors were also placed at 5 cm above the LES. Refluxate entry into the esophagus by MII criteria was determined relative to the onset of CC pressure wave. Esophageal lumen cross-sectional area (CSA) and muscle CSA during GER were determined from the US images. Eighty liquid GER episodes identified using MII criteria, of which 55 were clearly associated with CC pressure waves, were analyzed. The GER reached 15 cm above LES in 49 of 55 (89%) by MII criteria, but the CC pressure wave was observed at 5 and 15 cm during all episodes. The propagation of the CC pressure wave was simultaneous between 5 and 15 cm during 49 of 55 (89%) of the GER episodes, but reflux entry by MII criteria was retrograde during 53 of 55 (96%) of these episodes. During 5 air-reflux episodes, MII showed a simultaneous reflux entry between the 5- and 15-cm site, however, the CC pressure preceded reflux entry during all of these episodes. There was poor correlation between the luminal CSA and the magnitude of CC pressure (R(2) = 0.144). US images revealed a close temporal correlation between CC pressure and the increase in esophageal muscle thickness and muscle CSA (markers of longitudinal muscle contraction). Disassociation between CC pressure and MII-detected reflux suggests that the onset of CC pressure is not due to GER. We speculate that longitudinal muscle contraction plays an important role in the genesis of CC pressure.     

Effect of prostaglandin E2 on esophageal motility in man.

Studies were performed to investigate the effect of prostaglandin E2 on esophageal motility in 12 healthy volunteers. PGE2 infusion caused a dose-dependent reduction in the lower esophageal sphincter pressure. The threshold dose was less than 0.05 mug-kg-1-min-1 and maximal reduction of pressure (60%) occurred with a dose of 0.4 mug-kg-1-min-1. In contrast to its effect on the lower esophageal sphincter, PGE2 did not alter the pressure in the upper esophageal sphincter. PGE2 did not influence resting esophageal pressures; the amplitude of peristaltic contractions was reduced in the lower but not in the upper part of the body of the esophagus. These studies show that in man PGE2 exerts selective inhibitory influence on the activity of the lower part of the esophagus and lower esophageal sphincter which are composed of smooth muscle fibers.     

Regional differences in L-type Ca2+ channel expression in feline lower esophageal sphincter

In humans and cats, muscle from the lower esophageal sphincter (LES) circular region exhibits greater spontaneous tone than LES sling muscle, whereas the sling muscle is much more responsive to cholinergic stimulation. Despite physiological and pharmacological evidence for the presence of L-type Ca2+ channel current (ICa,L) activity in LES circular muscle, the identity of this channel has not been demonstrated biochemically or electrophysiologically fingerprinted. Furthermore, there is no information on the channel's presence and role in the sling region of the LES. We hypothesized that regional differences in the expression of ICa,L between LES circular and sling muscles, if present, could contribute to the functional asymmetry observed within the LES. ICa,L expression was compared between circular and sling regions of the LES by Western blot analysis. The patch-clamp technique was used to study ICa,L. Muscle strip studies assessed ICa,L contribution to contractile activity. We found both protein expression of ICa,L and ICa,L density to be greater in LES circular muscle than sling muscle. ICa,L voltage- and time-dependent activation and inactivation curves were similar in cells from both regions. ICa,L blockade with nifedipine inhibited spontaneous tone and ACh-induced contractions only in circular muscle but was able to abolish depolarization (KCl)-induced contractions in both sling and circular muscles. In contrast, La3+ inhibited tone and ACh-induced contractions in muscles from both regions. Therefore, regional myogenic differences in ICa,L expression within the LES circular and sling muscle exist and provide one explanation for the differential contribution of sling and circular muscle to LES contractility.