Feline lower esophageal sphincter sling and circular muscles have different functional inhibitory neuronal responses

Abstract

The lower esophageal sphincter (LES) has a circular muscle component exhibiting spontaneous tone that is relaxed by nitric oxide (NO) and a low-tone sling muscle that contracts vigorously to cholinergic stimulation but with little or no evidence of NO responsiveness. This study dissected the responses of the sling muscle to nitrergic innervation in relationship to its cholinergic innervation and circular muscle responses. Motor responses were induced by electrical field stimulation (EFS; 1-30 Hz) of muscle strips from sling and circular regions of the feline LES in the presence of cholinergic receptor inhibition (atropine) or NO synthase inhibition [NG-nitro-L-arginine (L-NNA)+/-atropine]. This study showed the following. First, sling muscle developed less intrinsic resting tone compared with circular muscle. Second, with EFS, sling muscle contracted (most at <or=10 Hz), whereas circular muscle relaxed >50% by 5 Hz. Third, on neural blockade with atropine or L-NNA+/-atropine, 1) sling muscle, although predominantly influenced by excitatory cholinergic stimulation, had a small neural NO-mediated inhibition, with no significant non-NO-mediated inhibition and 2) circular muscle, although little affected by cholinergic influence, underwent relaxation predominantly by neural release of NO and some non-NO inhibitory influence (at higher EFS frequency). Fourth, the sling, precontracted with bethanecol, could relax with NO and some non-NO inhibition. Finally, the tension range of both muscles is similar. In conclusion, sling muscle has limited NO-mediated inhibition to potentially augment or replace sling relaxation effected by switching off its cholinergic excitation. Differences within the LES sling and circular muscles could provide new directions for therapy of LES disorders.

Vagal sensory innervation of the gastric sling muscle and antral wall: implications for gastro‐esophageal reflux disease?

“…Physiological 39,42–44 , electrophysiological 8,11,12,16 , and immunohistochemical 14 investigations of the sling and cooperative LES muscle fibers have been focused largely on understanding the motor control of the tissues. Neuropharmacological therapies for GERD are most commonly designed either to ameliorate symptoms (proton pump inhibitors, mucosal protectants, etc.)…”

Regulation of basal tone, relaxation and contraction of the lower oesophageal sphincter. Relevance to drug discovery for oesophageal disorders

“…Morphological studies mapping the regional distribution of myenteric neurons in the LOS showed a majority of inhibitory neurons in the clasp region. Unlike the inhibitory components, the cholinergic one is stronger in sling fibres ( L'Heureux et al , 2006 ; Farre et al , 2007a ). Similarly, the variation can be explained by different cholinergic innervation ( Yuan and Brookes, 1999 ) and/or different sensitivity of both sides of the LOS to muscarinic receptors agonists as it was commented above.…”

“…This effect seems to be species dependent. In cat, rat and human ( Gonzalez et al , 2004 ; L'Heureux et al , 2006 ; Farre et al , 2007b ), NOS inhibitors do not affect the ‘off’ contraction. In vivo experiments in opossums and cats showed that N G‐nitro‐ L ‐arginine (i.v.)…”

“…This phenomena was described in pigs ( Farre et al , 2004 ) and cats. EFS of different muscle strips from the LOS showed that in clasp fibres, there is a strong nitrergic ( L'Heureux et al , 2006 ; Farre et al , 2007a ) and an apamin‐sensitive component mediated by ATP. In contrast, this type of neurotransmission is reduced in sling fibres.…”

The Esophagiome: concept, status, and future perspectives

“…It has been recently recognized that three specialized groupings of muscle fibers underlie GES sphincteric function: a grouping of specialized circularly oriented smooth muscle fibers intrinsic to the esophageal wall normally 2–3 cm above the junction between the esophageal body and the gastric cardia, where lie two circularly oriented groupings of smooth muscle fibers at the upper margin of the gastric cardia. The neurophysiological control of tone in these two muscle groupings, and therefore the mechanophysiology, is very different from the intrinsic upper circular grouping . Complicating the sphincteric mechanophysiology further, there is a source of contact pressure external to the esophageal wall supplied by a grouping of skeletal diaphragmatic crural muscle fibers that angulate around the external esophagus from the inferior surface of the costal diaphragm connecting at the vertebrae.…”