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Mittal RK. Motor Function of the Pharynx, Esophagus, and its Sphincters. San Rafael (CA): Morgan & Claypool Life Sciences; 2011.

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Motor Function of the Pharynx, Esophagus, and its Sphincters.

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Lower Esophageal Sphincter

LES is a unique muscle; it has its own myogenic tone that is modulated by neural, hormonal and paracrine factors [181,182]. Evidence for the myogenic stone comes from following in vitro and in vivo observations: (1) LES muscle strips, devoid of extrinsic innervations and studied in vitro (under no influence of hormonal factors) show steeper length tension characteristics than the muscle strips from the esophagus [183]. TTX which abolishes all intrinsic neural activity does not abolish tone in these muscle strips. In the presence of TTX, nitric oxide and other agents that act directly on the muscle reduce LES muscle tone [184]. (2) TTX does not abolish LES pressure in the in vivo studies [185]. Myogenic elements responsible for LES tone maintenance may be due to differences in the structural protein, LES has proportionally more α-actin and basic essential light chains LC17b, and less of a seven amino acid-inserted myosin isoform and caldesmon than the esophageal body circular muscle [186]. LES muscle utilizes more calcium from the intracellular than extracellular source as compared to the esophageal muscle [187]. There are also distinct intracellular signaling pathways in the LES as compared to the esophageal body [188]. From an electrophysiologic point of view, the LES muscle is in a state of greater depolarization than the esophageal muscle, as evidenced by a higher resting membrane potential than the esophagus [189]. The depolarized state of the sphincter muscle is suggested to be due to the resting chloride conductance [190]. Periodic spike bursts or increase in the depolarization results in an increase in the LES tonic activity. Tonic LES contraction is both spike dependent and spike independent [48]. Relative contribution of myogenic tone to the LES pressure differs in different species. In the opossum, myogenic tone dominates under basal resting condition. On the other hand, in cats [191], dogs [192], and humans [193], neural cholinergic drive contributes significantly to the basal LES tone. Atropine (15 μg/kg), which reduces excitatory neural cholinergic drive, reduces LES pressure by 50% to 70% in humans [194].

LES muscles are made up of clasp and sling fibers [57]—clasp fibers maintain stronger myogenic tone than the sling fibers [195] and sling fibers respond briskly to cholinergic agonist. Clasp fibers are predominantly innervated by inhibitory neurons located in the body of the esophagus and sling fibers by the excitatory neurons located in the stomach [73,196]. L-type calcium channels are predominantly seen in the clasp muscle fibers [197], and there are other differences as well in the mechanisms by which sling and clasp muscles contract and relax [198]. Differences in the properties of sling and clasp muscles fibers may be responsible for the greater pressure and greater cholinergic responsiveness of the LES pressure on the left side. Sling fibers are likely to be responsible for the maintenance of angle of HIS and flap valve function, both of which are considered to be important in the prevention of reflux.

Myenteric plexus contains both excitatory and inhibitory neurons that have intrinsic activity and are also under the influence of extrinsic vagus and spinal nerves. Excitatory neurons contain acetylcholine and substance P; inhibitory neurons, on the other hand, contain VIP and NO. Electrical stimulation of the LES muscle strip that supposedly stimulates both excitatory and inhibitory neurons elicits relaxation, suggesting that inhibitory influence dominates over the excitatory one. Stimulation of the vagus and spinal nerve has opposite effects on the LES pressure. Vagus nerve, which contains fibers that are thought to innervate both excitatory and inhibitory nerves, elicits relaxation only when electrically stimulated [199]. The inhibitory effect is frequency (dose) dependent, and none of the stimulus parameters induces LES contraction. The above not mean that vagus does not innervate excitatory neurons to the LES, it may be that when all, i.e., both inhibitory and excitatory vagus nerves fibers, are stimulated, inhibitory influence dominates, just like in vitro muscle strip studies [200]. Motor neurons that supply LES show topographical localization in the DMV. Stimulation of the rostral neurons elicits LES contraction and caudal cause LES relaxation, both of these effects are blocked by bilateral vagotomy [201]. The above observation suggests that vagus nerve contains fibers that impinge specifically on either the excitatory or the inhibitory neurons. Electrical stimulation of the sympathetic nerves causes LES contraction that is mediated by α-adrenergic receptors [202,203]. It is likely that the sympathetic/spinal nerves innervate neurons rather than the muscles directly. β-adrenergic stimulation, on the other hand, leads to LES relaxation, an effect that could be mediated through β1, β2, or β3 receptor [204,205]. β3-receptor stimulation, unlike β1 and β2, does not cause any cardiovascular side effects, which could be relevant for the treatment of esophageal motor disorders and LES hypertension. A large number of neuropeptides, hormones, and paracrine substances modulate LES tone, either increase or decrease LES pressure, as shown in Table 1, but whether they play any physiological role is not clear. Studies in the past investigated the role of various different types of foods including alcohol, smoking, and caffeine on the basal LES pressure including their mechanism of action, in the hope of understanding how they may elicit gastroesophageal reflux.

Table 1. Effects of some hormones and putative neurotransmitters on the lower esophageal sphincter and the possible sites of action: From the article Sphincter mechanisms at the lower end of the esophagus.

Table 1

Effects of some hormones and putative neurotransmitters on the lower esophageal sphincter and the possible sites of action: From the article Sphincter mechanisms at the lower end of the esophagus. Ravinder K. Mittal and Raj K. Goyal; GI Motility online (more...)

Long-term recordings in the animals and humans show fluctuations or phasic pressure changes in the LES. Some of these are related and others unrelated to the gastric component of the migrating myoelectrical complex (MMC) [206209]. During the first phase of MMC, the LES pressure is relatively stable, but during late phase II and throughout phase III, large-amplitude phasic contractions occur without a major change in the basal pressure. LES pressure increases before the increase in the gastric pressure. These MMC-related contractions are abolished by atropine and anesthesia [208,210]. Motilin, a neurohumoral agent released into circulation from the specialized cells in the wall of intestine, may be responsible for MMC-related phasic LES contractions [207]. LES also contracts in response to increases in intraabdominal pressure related to abdominal compression or straight leg raise, most likely through a vago-vagal reflex [194,211].

Copyright © 2011 by Morgan & Claypool Life Sciences.
Bookshelf ID: NBK54269
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