ATP and Odor Mixture Activate TRPM5-Expressing Microvillous Cells and Potentially Induce Acetylcholine Release to Enhance Supporting Cell Endocytosis in Mouse Main Olfactory Epithelium

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dc.contributor.authorFu, Ziying
dc.contributor.authorOgura, Tatsuya
dc.contributor.authorLuo, Wangmei
dc.contributor.authorLin, Weihong
dc.date.accessioned2018-04-09T15:00:38Z
dc.date.available2018-04-09T15:00:38Z
dc.date.issued2018
dc.description.abstractThe main olfactory epithelium (MOE) functions to detect odor molecules, provide an epithelial surface barrier, and remove xenobiotics from inhaled air. Mechanisms coordinating the activities of different cell types within the MOE to maintain these functions are poorly understood. Previously, we showed that superficially located microvillous cells (MCs) in the MOE expressing transient receptor potential channel M5 (TRPM5) are cholinergic and chemoresponsive and that they play an important role in maintaining odor responses and olfactory-guided behavior under challenging chemical environment. Here we investigated TRPM5-MC activation and subsequent paracrine regulation. Ca²⁺ imaging showed that TRPM5-MCs dose-dependently increase their intracellular Ca²⁺ levels in response to ATP, an important signaling molecule for airway mucociliary movement, and to an odor mixture. Pharmacological examination showed that the ATP responses are primarily mediated by P2X purinergic receptors. Interestingly, using the endocytosis dye pHrodo Red dextran, we found that chemical-activated TRPM5-MCs significantly increase the number of pHrodo-labeled puncta compared to controls without stimulation and compared to cells that do not respond to ATP or to the odor mixture. These results indicate potential vesicle recycling after release of the signaling molecule acetylcholine (ACh). Interestingly, TRPM5 knockout (KO) results in a decrease in ATP-induced pHrodo internalization. We further investigated cholinergic regulation of neighboring supporting cells (SCs). We found that ACh strongly elevates intracellular Ca²⁺ and potentiates pHrodo endocytosis in SCs. The ACh effects are diminished in the presence of atropine or M3 muscarinic receptor antagonist and in SCs lacking M3 receptors. Collectively, these data suggest that TRPM5-MCs may regulate the MOE’s multicellular network activity via cholinergic paracrine signaling for functional maintenance and adaptive plasticity.en_US
dc.description.sponsorshipWe thank Kayla Lemons and Abdullah Almatrouk for critically reading the manuscript.
dc.description.urihttps://www.frontiersin.org/articles/10.3389/fncel.2018.00071/fullen_US
dc.format.extent16 pagesen_US
dc.genrejournal articlesen_US
dc.identifierdoi:10.13016/M2HH6C76B
dc.identifier.citationFu Z, Ogura T, Luo W and Lin W (2018) ATP and Odor Mixture Activate TRPM5-Expressing Microvillous Cells and Potentially Induce Acetylcholine Release to Enhance Supporting Cell Endocytosis in Mouse Main Olfactory Epithelium. Front. Cell. Neurosci. 12:71. doi: 10.3389/fncel.2018.00071en_US
dc.identifier.urihttps://doi.org/10.3389/fncel.2018.00071
dc.identifier.urihttp://hdl.handle.net/11603/7926
dc.language.isoen_USen_US
dc.publisherFrontieren_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Biological Sciences Department Collection
dc.relation.ispartofUMBC Faculty Collection
dc.relation.ispartofUMBC Student Collection
dc.rightsThis item may be protected under Title 17 of the U.S. Copyright Law. It is made available by UMBC for non-commercial research and education. For permission to publish or reproduce, please contact the author.
dc.rightsAttribution 4.0 International*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.titleATP and Odor Mixture Activate TRPM5-Expressing Microvillous Cells and Potentially Induce Acetylcholine Release to Enhance Supporting Cell Endocytosis in Mouse Main Olfactory Epitheliumen_US
dc.typeTexten_US

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