title: The K+ channel KIR2.1 functions in tandem with proton influx to mediate sour taste transduction.
abstract: Sour taste is detected by a subset of taste cells on the tongue and palate epithelium that respond to acids with trains of action potentials. Entry of protons through a Zn(2+)-sensitive proton conductance that is specific to sour taste cells has been shown to be the initial event in sour taste transduction. Whether this conductance acts in concert with other channels sensitive to changes in intracellular pH, however, is not known. Here, we show that intracellular acidification generates excitatory responses in sour taste cells, which can be attributed to block of a resting K(+) current. We identify KIR2.1 as the acid-sensitive K(+) channel in sour taste cells using pharmacological and RNA expression profiling and confirm its contribution to sour taste with tissue-specific knockout of the Kcnj2 gene. Surprisingly, acid sensitivity is not conferred on sour taste cells by the specific expression of Kir2.1, but by the relatively small magnitude of the current, which makes the cells exquisitely sensitive to changes in intracellular pH. Consistent with a role of the K(+) current in amplifying the sensory response, entry of protons through the Zn(2+)-sensitive conductance produces a transient block of the KIR2.1 current. The identification in sour taste cells of an acid-sensitive K(+) channel suggests a mechanism for amplification of sour taste and may explain why weak acids that produce intracellular acidification, such as acetic acid, taste more sour than strong acids.
authors.affiliation: Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089;
authors.forename: Wenlei
authors.initials: W
authors.lastname: Ye
authors.affiliation: Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089;
authors.forename: Rui B
authors.initials: RB
authors.lastname: Chang
authors.affiliation: Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089;
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Bushman
authors.affiliation: Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089;
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Tu
authors.affiliation: Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089;
authors.forename: Eric M
authors.initials: EM
authors.lastname: Mulhall
authors.affiliation: Department of Otolaryngology, University of Colorado Medical School, Aurora, CO 80045; Rocky Mountain Taste and Smell Center, University of Colorado Medical School, Aurora, CO 80045;
authors.forename: Courtney E
authors.initials: CE
authors.lastname: Wilson
authors.affiliation: Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089;
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Cooper
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado Medical School, Aurora, CO 80045;
authors.forename: Wallace S
authors.initials: WS
authors.lastname: Chick
authors.affiliation: Department of Pharmacology, University of Vermont, Burlington, VT 05405;
authors.forename: David C
authors.initials: DC
authors.lastname: Hill-Eubanks
authors.affiliation: Department of Pharmacology, University of Vermont, Burlington, VT 05405; Institute of Cardiovascular Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Nelson
authors.affiliation: Department of Otolaryngology, University of Colorado Medical School, Aurora, CO 80045; Rocky Mountain Taste and Smell Center, University of Colorado Medical School, Aurora, CO 80045;
authors.forename: Sue C
authors.initials: SC
authors.lastname: Kinnamon
authors.affiliation: Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089; liman@USC.edu.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Liman
mesh_terms: D000143:Acids / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019426:Integrases / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D018345:Mice, Knockout; D008954:Models, Biological; D009928:Organ Specificity / Q000187:drug effects; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D011522:Protons; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D050053:TRPM Cation Channels / Q000378:metabolism; D013649:Taste / Q000187:drug effects / Q000502:physiology*; D013650:Taste Buds / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology
chemical_list: D000143:Acids; D015220:Calcium Channels; C489461:Kir2.1 channel; C486487:Pkd2l1 protein, mouse; D024661:Potassium Channels, Inwardly Rectifying; D011522:Protons; D011956:Receptors, Cell Surface; D050053:TRPM Cation Channels; C498617:Trpm5 protein, mouse; C045073:Cre recombinase; D019426:Integrases; D015032:Zinc
keywords: gustatory; inward rectifier; potassium channel; proton channel; taste cell