GABA expression in the mammalian taste bud functions as a route of inhibitory cell-to-cell communication

• Published in: Proceedings of the National Academy of Sciences - PNAS 2009-03, Vol.106 (10), p.4006-4011
• Main Authors: Cao, Yu, Zhao, Fang-li, Kolli, Tamara, Hivley, Randy, Herness, Scott
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Biological Sciences; Cell Communication - drug effects; Cells; Cellular immunity; Chloride Channels - metabolism; Chlorides; GABA-A Receptor Agonists; gamma-Aminobutyric Acid - metabolism; Gene expression; Gene Expression Regulation - drug effects; Genotype & phenotype; Glutamate Decarboxylase - metabolism; Gustatory perception; Immunocytochemistry; Ion Channel Gating - drug effects; Mammals; Muscimol - pharmacology; Neurons; Neurotransmitters; Peptides; Potassium Channels - metabolism; Protein Subunits - genetics; Protein Subunits - metabolism; Proteins; Rats; Rats, Sprague-Dawley; Receptors; Receptors, GABA-A - genetics; Receptors, GABA-A - metabolism; Receptors, GABA-B - genetics; Receptors, GABA-B - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Taste buds; Taste Buds - cytology; Taste Buds - drug effects; Taste Buds - enzymology; Taste Buds - metabolism; Taste cells
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0808672106

Recent advances have underscored cell-to-cell communication as an important component of the operation of taste buds with individual taste receptor cells (TRCs) communicating with one another by means of a number of neurotransmitters and neuropeptides, although functional roles are not yet understood. Here, we characterize the presence, distribution pattern, phenotype, and functional consequences of a previously undescribed inhibitory route within the taste bud mediated by the classic neurotransmitter GABA and its receptors. By using immunocytochemistry, subsets of TRCs within rat taste buds were identified as expressing GABA, and its synthetic enzyme glutamate decarboxylase (GAD). GAD expression was verified with Western blotting. Immunofluorescent studies revealed complex coexpression patterns of GAD with the TRC protein markers gustducin, neural cell adhesion molecule, protein gene product 9.5, and synaptosomal-associated protein of 25 kDa that collectively outline hardwired signaling pathways of GABAergic TRCs. RT-PCR and immunocytochemistry demonstrated that both GABAA and GABAB receptors are expressed in the taste bud. The later was observed in a subset TRCs paracrine to GAD-expressing TRCs. Physiological effects of GABA were examined by patch clamp recordings. GABA and the GABAA agonists muscimol and isoguvacine enhanced isolated chloride currents in a dose-dependent manner. Also, GABA and the GABAB agonist baclofen both elicited increases of the inwardly rectifying potassium currents that could be blocked by the GABAB receptor antagonist CGP 35348 and the G protein blocker GDP-βS. Collectively, these data suggest that GABAergic TRCs are able to shape the final chemosensory output of the bud by means of processes of cell-to-cell modulation.