Nasal Solitary Chemoreceptor Cell Responses to Bitter and Trigeminal Stimulants In Vitro

• Published in: Journal of neurophysiology 2008-06, Vol.99 (6), p.2929-2937
• Main Authors: Gulbransen, Brian D, Clapp, Tod R, Finger, Thomas E, Kinnamon, Sue C
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - pharmacology; Animals; Calcium - metabolism; Chemoreceptor Cells - physiology; Estrenes - pharmacology; Green Fluorescent Proteins - biosynthesis; Green Fluorescent Proteins - genetics; In Vitro Techniques; Isotonic Solutions - pharmacology; Mice; Mice, Transgenic; Nasal Cavity - cytology; Phenylthiourea - pharmacology; Phosphodiesterase Inhibitors - pharmacology; Pyrrolidinones - pharmacology; Quaternary Ammonium Compounds - pharmacology; Stimulation, Chemical; Taste - physiology; Transducin - metabolism; Trigeminal Nerve - physiology; TRPM Cation Channels - genetics
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00066.2008

1 Rocky Mountain Taste and Smell Center; 2 Department of Cell and Developmental Biology, Neuroscience Program, University of Colorado Denver School of Medicine, Aurora; and 3 Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado Submitted 18 January 2008; accepted in final form 4 April 2008 Nasal trigeminal chemosensitivity in mice and rats is mediated in part by epithelial solitary chemoreceptor (chemosensory) cells (SCCs), but the exact role of these cells in chemoreception is unclear. Histological evidence suggests that SCCs express elements of the bitter taste transduction pathway including T2R (bitter taste) receptors, the G protein -gustducin, PLCβ2, and TRPM5, leading to speculation that SCCs are the receptor cells that mediate trigeminal nerve responses to bitter taste receptor ligands. To test this hypothesis, we used calcium imaging to determine whether SCCs respond to classic bitter-tasting or trigeminal stimulants. SCCs from the anterior nasal cavity were isolated from transgenic mice in which green fluorescent protein (GFP) expression was driven by either TRPM5 or gustducin. Isolated cells were exposed to a variety of test stimuli to determine which substances caused an increase in intracellular Ca 2+ ([Ca 2+ ] i ). GFP-positive cells respond with increased [Ca 2+ ] i to the bitter receptor ligand denatonium and this response is blocked by the PLC inhibitor U73122. [GenBank] In addition, GFP+ cells respond to the neuromodulators adenosine 5'-triphosphate and acetylcholine but only very rarely to other bitter-tasting or trigeminal stimuli. Our results demonstrate that TRPM5- and gustducin-expressing nasal SCCs respond to the T2R agonist denatonium via a PLC-coupled transduction cascade typical of T2Rs in the taste system. Address for reprint requests and other correspondence: B. D. Gulbransen, University of Colorado Denver School of Medicine, Department of Cell and Developmental Biology, Neuroscience Program, Aurora, CO 80045 (E-mail: bgulbran{at}ucalgary.ca )