Multifunctional rapidly adapting mechanosensitive enteric neurons (RAMEN) in the myenteric plexus of the guinea pig ileum.

摘要

An important feature of the enteric nervous system (ENS) is its capability to respond to mechanical stimulation which, as currently suggested for the guinea-pig ileum, is encoded by specialized intrinsic primary afferent neurons (IPANs). We used von Frey hairs or intraganglionic volume injections to mimic ganglion deformation as observed in freely contracting preparations. Using fast voltage-sensitive dye imaging we identified rapidly adapting mechanosensitive enteric neurons (RAMEN, 25% of all neurons) in the myenteric plexus of the guinea pig ileum. RAMEN responded with phasic spike discharge to dynamic changes during ganglion deformation. This response was reproducible and increased with increasing forces. Deformation-evoked spike discharge was not changed by synaptic blockade with hexamethonium, omega-conotoxin or low Ca(2+)/high Mg(2+), defunctionalization of extrinsic afferents with capsaicin or muscle paralysis with nifedipine, suggesting direct activation of RAMEN. All RAMEN received hexamethonium-sensitive fast EPSPs, which were blocked by omega-conotoxin and low Ca(2+)/high Mg(2+). Seventy-two per cent of RAMEN were cholinergic, 22% nitrergic, and 44% were calbindin and NeuN negative, markers used to identify IPANs. Mechanosensitivity was observed in 31% and 47% of retrogradely traced interneurons and motor neurons, respectively. RAMEN belong to a new population of mechanosensitive neurons which differ from IPANs. We provided evidence for multifunctionality of RAMEN which may fulfil sensory, integrative and motor functions. In light of previously identified mechanosensitive neuron populations, mechanosensitivity appears to be a property of many more enteric neurons than generally assumed. The findings call for a revision of current concepts on sensory transmission within the ENS.