Polarized intrinsic neural reflexes in response to colonic elongation

Abstract

Propulsion in both small and large intestine is largely mediated by the peristaltic reflex; despite this, transit through the shorter colon is at least 10 times slower. Recently we demonstrated that elongating a segment of colon releases nitric oxide (NO) to inhibit peristalsis. The aims of this study were to determine if colonic elongation was physiologically significant, and whether elongation activated polarized intrinsic neural reflexes. Video imaging monitored fecal pellet evacuation from isolated guinea-pig colons full of pellets. Recordings were made from the circular muscle (CM) and longitudinal muscle (LM) in flat sheet preparations using either intracellular microelectrode or Ca 2+ imaging techniques. Full colons were 158.1 ± 6.1% longer than empty colons. As each pellet was expelled, the colon shortened and pellet velocity increased exponentially (full 0.34, empty 1.01 mm s −1 ). In flat sheet preparations, maintained circumferential stretch generated ongoing peristaltic activity (oral excitatory and anal inhibitory junction potentials) and Ca 2+ waves in LM and CM. Colonic elongation (140% of its empty slack length) applied oral to the recording site abolished these activities, whereas anal elongation significantly increased the frequency and amplitude of ongoing peristaltic activity. Oral elongation inhibited the excitation produced by anal elongation; this inhibitory effect was reversed by blocking NO synthesis. Pelvic nerve stimulation elicited polarized responses that were also suppressed by NO released during colonic elongation. In conclusion, longitudinal stretch excites specific mechosensitive ascending and descending interneurons, leading to activation of polarized reflexes. The dominance of the descending inhibitory reflex leads to slowed emptying of pellets in a naturally elongated colon.

P2Y1 Receptors Mediate Apamin-Sensitive and -Insensitive Inhibitory Junction Potentials in Murine Colonic Circular Smooth Muscle

“…Orientation of the tissues was not specified in the aforementioned reports. Zhang and Paterson (2005) and Dickson et al (2008) have described polarized intrinsic innervation to the intestinal smooth muscle. Our finding that a major component of the apaminresistant IJP was produced predominantly by circumferential and oral but not by aboral NS (Table 3) suggests that purinergic nerve fibers that project circumferentially and orally produce apamin-sensitive and -resistant IJPs, whereas those that project aborally induce apamin-sensitive IJPs.…”

Inhibitory motor neurons of the esophageal myenteric plexus are mechanosensitive

“…Pharmacological analysis of in vivo studies suggests that esophageal motor neurons might be mechanosensitive (22); however, this novel notion needs direct evidence. Moreover, although a growing body of literature suggests that enteric neurons respond directly to mechanical stretch in the small intestine and colon (6,28,36,41), whether isolated enteric neurons are mechanosensitive has not been studied. Recently, we successfully cultured myenteric neurons from the rat esophagus (9).…”

Colonic Migrating Motor Complexes, High Amplitude Propagating Contractions, Neural Reflexes and the Importance of Neuronal and Mucosal Serotonin

“…These particular interneurons release nitric oxide (NO) to depress myenteric neurons underlying the CMMC and peristalsis. 69,76,77 Blocking NO synthesis in healthy humans increases the number of propagating contractions. 68 Furthermore, flushing the human colon increases the number of HAPCs.…”

“…63,72 Their rarity may be due to myenteric neurons being normally inhibited by sympathetic nervous activ- ity 63,[73][74][75] or the intrinsic occult inhibitory neural reflex. 69,76,77 The occult inhibitory reflex is triggered by colonic elongation caused by the accumulation of fecal matter. 69,76 Colonic elongation activates mainly long descending mechanosensitive nNOS positive sensory interneurons that are triggered by longitudinal stretch.…”

“…69,76,77 The occult inhibitory reflex is triggered by colonic elongation caused by the accumulation of fecal matter. 69,76 Colonic elongation activates mainly long descending mechanosensitive nNOS positive sensory interneurons that are triggered by longitudinal stretch. These particular interneurons release nitric oxide (NO) to depress myenteric neurons underlying the CMMC and peristalsis.…”