Voltage-gated sodium channels in taste bud cells.
BACKGROUND
Taste bud cells transmit information regarding the contents of food from taste receptors embedded in apical microvilli to gustatory nerve fibers innervating basolateral membranes. In particular, taste cells depolarize, activate voltage-gated sodium channels, and fire action potentials in response to tastants. Initial cell depolarization is attributable to sodium influx through TRPM5 in sweet, bitter, and umami cells and an undetermined cation influx through an ion channel in sour cells expressing PKD2L1, a candidate sour taste receptor. The molecular identity of the voltage-gated sodium channels that sense depolarizing signals and subsequently initiate action potentials coding taste information to gustatory nerve fibers is unknown.


RESULTS
We describe the molecular and histological expression profiles of cation channels involved in electrical signal transmission from apical to basolateral membrane domains. TRPM5 was positioned immediately beneath tight junctions to receive calcium signals originating from sweet, bitter, and umami receptor activation, while PKD2L1 was positioned at the taste pore. Using mouse taste bud and lingual epithelial cells collected by laser capture microdissection, SCN2A, SCN3A, and SCN9A voltage-gated sodium channel transcripts were expressed in taste tissue. SCN2A, SCN3A, and SCN9A were expressed beneath tight junctions in subsets of taste cells. SCN3A and SCN9A were expressed in TRPM5 cells, while SCN2A was expressed in TRPM5 and PKD2L1 cells. HCN4, a gene previously implicated in sour taste, was expressed in PKD2L1 cells and localized to cell processes beneath the taste pore.


CONCLUSIONS
SCN2A, SCN3A and SCN9A voltage-gated sodium channels are positioned to sense initial depolarizing signals stemming from taste receptor activation and initiate taste cell action potentials. SCN2A, SCN3A and SCN9A gene products likely account for the tetrodotoxin-sensitive sodium currents in taste receptor cells.
Gao
Na
N
Senomyx, Inc, 4767 Nexus Centre Drive, San Diego, CA 92121, USA. na.gao@senomyx.com
Lu
Min
M
Echeverri
Fernando
F
Laita
Bianca
B
Kalabat
Dalia
D
Williams
Mark E
ME
Hevezi
Peter
P
Zlotnik
Albert
A
Moyer
Bryan D
BD
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D062551:NAV1.2 Voltage-Gated Sodium Channel; D062552:NAV1.3 Voltage-Gated Sodium Channel; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000378:metabolism; D013649:Taste / Q000502:physiology; D013650:Taste Buds / Q000378:metabolism*; D014059:Tongue / Q000378:metabolism
D015220:Calcium Channels; D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D062551:NAV1.2 Voltage-Gated Sodium Channel; D062552:NAV1.3 Voltage-Gated Sodium Channel; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568253:Scn2A protein, rat; C000654500:Scn2a protein, mouse; C478638:Scn3a protein, rat; C503479:Scn9a protein, mouse; D015222:Sodium Channels; D050053:TRPM Cation Channels