Mittal RK. Inhibitory motor neurons of the esophageal myenteric plexus are mechanosensitive. Am J Physiol Cell Physiol 308: C405-C413, 2015. First published December 24, 2014; doi:10.1152/ajpcell.00159.2014.-Mechanosensitivity of enteric neurons has been reported in the small intestine and colon, but not in the esophagus. Our earlier in vivo studies show that mechanical stretch of the esophagus in the axial direction induces neurally mediated relaxation of the lower esophageal sphincter, possibly through mechanosensitive motor neurons. However, this novel notion that the motor neurons are mechanosensitive has not been examined in isolated esophageal myenteric motor neurons. The goal of our present study was to examine the mechanosensitivity of esophageal motor neurons in primary culture and elucidate the underlying molecular mechanisms. Immmunocytochemical analysis revealed that Ͼ95% cells were positive for the neuronal marker protein gene product 9.5 and that 66% of these cells costained with protein gene product 9.5 and neuronal nitric oxide (NO) synthase. Hypotonic solution induced an increase in the cytoplasm volume in all cells that was independent of extracellular Ca 2ϩ . Hypotonic solution and mechanical stretch induced cytoplasmic free Ca 2ϩ signaling in ϳ65% of neurons in the presence, but not absence, of extracellular Ca 2ϩ . Neurons grown on the elastic membrane responded to mechanical stretch by an increase in neuronal size and Ca 2ϩ signaling simultaneously. Hypotonic stretch-induced cytoplasmic free Ca 2ϩ signaling was not affected by extracellular Mg 2ϩ , 5-nitro-2-(3-phenylpropylamino)benzoic acid, and nifedipine but was attenuated by 2-aminoethoxydiphenyl borate, Gd 3ϩ , and Grammostola mechanotoxin 4, blockers of the stretch-activated ion channels. In ϳ57% of the neurons, hypotonic stretch also induced Ca 2ϩ -dependent cytoplasmic NO production, which was abolished by Grammostola mechanotoxin 4. These results prove that the esophageal inhibitory motor neurons possess a mechanosensitive property and also provide novel insights into the stretch-activated ion channel-Ca 2ϩ -NO signaling pathway in these neurons. neuronal nitric oxide synthase; nitric oxide production; cytoplasmic free calcium; stretch-activated cation channels THE ENTERIC NERVOUS SYSTEM regulates gastrointestinal (GI) functions, such as digestion, absorption, secretion, motility, and sensation (1, 14, 37). The enteric nervous system contains three types of neurons: 1) sensory neurons [intrinsic primary afferent neurons (IPANs)], 2) interneurons, and 3) motor neurons (1, 14). The latter are further subdivided into excitatory and inhibitory motor neurons on the basis of their regulatory functions (1, 15): excitatory motor neurons contain neurotransmitters, such as acetylcholine, substance P, and glutamate (14), and inhibitory motor neurons contain nitric oxide (NO), ATP, and vasoactive intestinal polypeptide (14, 37).Similar to neurons in the rest of the GI tract, neurons in the wall of esophagus also play an important role in the s...

Although the occlusal vertical dimension (OVD) is strictly controlled, the neuronal mechanism of its regulation is still unclear. We hypothesize that neurons in the trigeminal mesencephalic nucleus (MesV) play an important role in the regulation of the OVD, because the MesV receives the projection from jaw-closing muscle spindles and periodontal mechanoreceptors. We measured the temporal OVD change in the guinea pig to study the effects of MesV lesions on the OVD. OVD-raised animals without MesV lesions showed a rapid OVD decrease to the same level as that in naïve controls, followed by an OVD increase after the OVD-raising appliance was removed. In contrast, OVD-raised animals with MesV lesions showed only a slight decrease in the OVD for 15 days after removal of the appliance, and then the OVD increased. The time-course of OVD development in normal-bite animals with MesV lesions was similar to that of naïve controls. These results suggest that MesV neurons are involved in OVD regulation.

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