Mechanisms of mechanotransduction by specialized low-threshold mechanoreceptors in the guinea pig rectum

Abstract

The guinea pig rectum, but not the colon, is innervated by a specialized class of distension-sensitive mechanoreceptors that have transduction sites corresponding to rectal intraganglionic laminar endings (rIGLEs). Rectal mechanoreceptors recorded in vitro had low threshold to circumferential stretch, adapted slowly, and could respond within 2 ms to mechanical stimulation by a piezo-electric probe. Antagonists to ionotropic N-methyl-D-aspartate (NMDA; CGS 19755, memantine) and non-NMDA (6,7-dinitroquinoxaline-2,3-dione) glutamate receptors did not affect mechanotransduction. In normal Krebs solution, the P2X purinoreceptor agonist alpha,beta-methylene ATP reduced mechanoreceptor firing evoked by distension but simultaneously relaxed circular smooth muscle and inhibited stretch-induced contractions. Neither ATP nor alpha,beta-methylene ATP affected mechanotransduction when transduction sites were directly compressed with von Frey hairs. The P2 purinoreceptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid did not affect stretch-induced firing but reduced the inhibitory effect of alpha,beta-methylene ATP on stretch-induced firing. Under isometric conditions, blocking synaptic transmission in Ca2+-free solution reduced stretch-evoked firing but not when basal tension was restored to control levels. Under isotonic condition, Ca2+-free solution did not significantly affect load-evoked firing. The blockers of mechanogated and/or transient receptor potential channels, benzamil, Gd3+, SKF 96365, and ruthenium red inhibited stretch-induced firing but, in parallel, significantly reduced stretch-induced contractions. Benzamil and SKF 96365 were able to inhibit mechanotransduction when transduction sites were compressed with von Frey hairs. The results show that mechanotransduction is rapid but does not depend on fast exocytotic release of mediators. It is likely that stretch-activated ion channels on rIGLEs are involved in direct, physical mechanotransduction by rectal low-threshold mechanoreceptors.

Differential roles of stretch-sensitive pelvic nerve afferents innervating mouse distal colon and rectum

“…Of the four groups, the accelerating stretch-response function of rectal muscular afferents significantly differed from the other three groups, of which none differed from each other. In related studies, the guinea pig rectum was reported to be densely innervated by a distinct population of LT, slowly adapting mechanoreceptors with specialized intraganglionic laminar endings (IGLEs), representing a group of afferent endings not found more proximally in the colon (22,41). Rectal IGLEs, which have not been described in the mouse, terminate in the myenteric plexus between circular and longitudinal muscle layers (22); they would likely have been categorized functionally as rectal muscular afferents in the present study.…”

Identification of different functional types of spinal afferent neurons innervating the mouse large intestine using a novel CGRPα transgenic reporter mouse

“…In the present study, HF afferents were the most sensitive and rapidly firing class. This profile suggests that their peripheral terminals may be rectal IGLEs (33,34,65). They fire to small amounts of stretch and continue to encode without saturating to distensions into the noxious range (64).…”

Locality-dependent descending reflex motor activity in the anal canal–cholinergic and nitrergic contributions in the rat model

“…Rectal wall distension is a factor that influences the excitation of mechanoceptors that are involved in monitoring the filling state and the contraction level of the rectum in humans and cats [24,25] . Detection of mechanical deformation by mechanoceptors containing specialized intraganglionic laminal endings, which are found in dense afferent innervations, has been described in the guinea pig rectum [26,27] . Rectal contentinduced stretching of the rectal wall is sufficient to initiate the defecation reflex in humans [28] .…”