Intramural mechanism of esophageal peristalsis: roles of cholinergic and noncholinergic nerves.

Abstract

We examined the role of peripheral cholinergic and noncholinergic mechanisms in esophageal peristalsis. Intramural nerve elements in rings of circular muscle from six different levels of the opossum esophagus were stimulated transmurally so as to cause neurally mediated muscle contractions. Stimulus frequency was varied from 2 to 40 Hz. An increase in stimulus frequency caused an increase in latencies of contractions in rings from distal esophageal sites and a decrease in latencies in rings from proximal sites. This resulted in a marked slowing of the calculated peristaltic speed. Increasing stimulus frequency also caused an increase in duration and amplitude of contractions. These effects were reversed by atropine (0.1 ,uM), suggesting that higher stimulus frequencies recruited more cholinergic nerves. In the presence of atropine, increasing the stimulus frequency caused an increase in latencies of contraction at all sites, suggesting that increasing stimulation frequency applied to noncholinergic nerves causes an increase in latencies of contraction at all sites. The results of this study indicate that both noncholinergic and cholinergic nerves play a role in the peripheral mechanism of esophageal peristalsis. Cholinergic nerve stimulation reduces the latency and enhances the amplitude and duration of contractions seen with noncholinergic nerve stimulation alone. The influence of cholinergic innervation is most prominent proximally and decreases distally along the smooth muscle portion of the esophagus. This peripherally located gradient of cholinergic innervation plays an important role in determining the speed and amplitude of esophageal peristalsis.The act of swallowing is associated with a peristaltic wave of esophageal contractions. This peristaltic activity in the skeletal muscle portion of the esophagus is due to sequential activation of lower muscle neurons in the vagal nuclei (1, 2). However, in the smooth muscle portion, this peristaltic activity may be due to peripheral intramural mechanisms (1, 2). This is evidenced by studies showing the following. (i) After bilateral vagotomy, balloon distension in the esophagus causes peristalsis in the smooth muscle portion (secondary peristalsis) (2,3). (ii) In vitro transmural stimulation of circular muscle strips from different esophageal levels shows that strips from more proximal sites have shorter latencies of contraction than strips from more distal sites (4). (iii) Electrical stimulation of the peripheral end of the decentralized vagus nerve causes peristaltic contractions in the smooth muscle portion of the esophagus (5, 6). In addition, the speed and polarity of peristalsis can be modified by altering the parameters of the electrical stimuli applied to the decentralized vagal nerves (6), thereby demonstrating that peripheral mechanisms possess the ability to modulate the speed of esophageal peristalsis.The nature of the nerves involved in the peripheral regulation of peristalsis is not fully known. It has been suggested by some investigators t...

Regional functional specialization and inhibitory nitrergic and nonnitrergic coneurotransmission in the human esophagus

“…Animal studies described that NO released from inhibitory myenteric neurons controlled both the amplitude and the latency timing of the off-response in the distal smooth muscle esophagus (5) and mediated nerve-induced hyperpolarization of circular esophageal and LES smooth muscle (4, 6). These in vitro animal studies also found that inhibition of NOS with L-NNA or by blocking the NO-intracellular pathway with the guanylate cyclase inhibitor 1H- [1,2,4]oxadiazolo- [4,3-a]quinoxalin-1-one attenuated or even abolished the off-response and shortened the latency period, inducing the appearance of a cholinergic on-contraction of greater amplitude than the previous on-and off-contractions (5,20). In our human study, in vitro on and off EB contractions are similar to these previous in vitro animal studies and to the two types of esophageal peristaltic contractions found during in vivo vagal stimulation in the opossum esophagus (20).…”

“…Two different protocols with different EFS parameters were performed during electrophysiological studies. The first protocol consisted of an electrical stimulus with the following characteristics: total duration, 100 ms; frequency, 20 Hz; pulse duration, 0.3 ms; and increasing amplitude voltage, 5,10,12,15,17,20,25,30, and 50 V. The amplitude and the duration of EFS-induced IJP were measured under control conditions and after addition of each drug. Second, longer pulses of 5 s at supramaximal voltage of 50 V and pulse duration of 0.3 ms were performed at 1 Hz (5 pulses) and 5 Hz (25 pulses).…”

“…Animal studies found cholinergic nerve stimulation enhanced the amplitude and duration of esophageal peristalsis, with the influence of cholinergic EMNs being most prominent proximally along the smooth muscle portion of the esophagus (5). Human studies showed that activation of inhibitory EMNs preceded that of cholinergic EMNs during EB peristalsis (30).…”

MLCK and PKC Involvements via Gi and Rho A Protein in Contraction by the Electrical Field Stimulation in Feline Esophageal Smooth Muscle

“…The incidence of various patterns of responses by EFS in esophageal smooth muscle in vitro, which are composed of on-and off-contractions, differ at esophageal sites and are dependent on stimulation frequencies. These events result from the influence of the integration of intramural excitatory cholinergic and NANC inhibitory nitrergic nerves, which innervate esophageal smooth muscle [4,11]. In addition, ion currents generated via 4-AP-sensitive voltage-dependent K ＋ channels in muscle might participate in EFS-induced responses [12].…”

“…Acetylcholine (ACh) is an excitatory neurotransmitter that regulates esophageal motor function, although there are regional and species differences in the relative contributions made by cholinergic mechanisms to esophageal peristalsis [3][4][5], and stimulation of nerves in the esophagus induces NO-mediated hyperpolarization and relaxation [6,7].…”