Affiliation:
1. Division of Gastroenterology, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, California; and Veterans Affairs San Diego Healthcare System, San Diego, California
Abstract
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 >95% 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 Ca2+. Hypotonic solution and mechanical stretch induced cytoplasmic free Ca2+ signaling in ∼65% of neurons in the presence, but not absence, of extracellular Ca2+. Neurons grown on the elastic membrane responded to mechanical stretch by an increase in neuronal size and Ca2+ signaling simultaneously. Hypotonic stretch-induced cytoplasmic free Ca2+ signaling was not affected by extracellular Mg2+, 5-nitro-2-(3-phenylpropylamino)benzoic acid, and nifedipine but was attenuated by 2-aminoethoxydiphenyl borate, Gd3+, and Grammostola mechanotoxin 4, blockers of the stretch-activated ion channels. In ∼57% of the neurons, hypotonic stretch also induced Ca2+-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-Ca2+-NO signaling pathway in these neurons.
Publisher
American Physiological Society
Cited by
26 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献