title: Mechanism of the excitatory Cl- response in mouse olfactory receptor neurons.
abstract: In vertebrate olfactory receptor neurons (ORNs), the odorant-triggered receptor current flows through two distinct ion channels on the sensory cilia: Ca2+ influx through a cyclic nucleotide-gated (CNG) channel followed by Cl- efflux through a Ca2+-activated anion channel. The excitatory Cl- current amplifies the small CNG current and crucially depends on a high intracellular Cl- concentration. We show here that a (Na+)-(K+)-(2Cl-) cotransporter, NKCC1, is required for this Cl- current, in that ORNs deficient in Nkcc1 or incubated with an NKCC blocker (bumetanide) lack the Cl- current. Surprisingly, immunocytochemistry indicates that NKCC1 is located on the somata and dendrites of ORNs rather than the cilia, where transduction occurs. This topography is remarkably similar to the situation in secretory epithelial cells, where basolateral Cl- uptake and apical Cl- efflux facilitate transepithelial fluid movement. Thus, a single functional architecture serves two entirely different purposes, probably underscoring the epithelial origin of the ORNs.
authors.affiliation: Department of Neuroscience, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA. jreisert@jhmi.edu
authors.forename: Johannes
authors.initials: J
authors.lastname: Reisert
authors.forename: Jun
authors.initials: J
authors.lastname: Lai
authors.forename: King-Wai
authors.initials: KW
authors.lastname: Yau
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bradley
mesh_terms: D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002034:Bumetanide / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D018118:Chloride Channels / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism* / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005697:Galactosides / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007211:Indoles / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009544:Niflumic Acid / Q000494:pharmacology; D009831:Olfactory Mucosa / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D010812:Physical Stimulation / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1; D064506:Solute Carrier Family 12, Member 2
chemical_list: D000447:Aldehydes; D018118:Chloride Channels; D002712:Chlorides; D054815:Cyclic Nucleotide-Gated Cation Channels; D005697:Galactosides; D007211:Indoles; D007473:Ion Channels; D012333:RNA, Messenger; C578715:Slc12a1 protein, mouse; C578878:Slc12a2 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D064506:Solute Carrier Family 12, Member 2; D002034:Bumetanide; C007293:DAPI; D009544:Niflumic Acid; C046204:heptanal; D000242:Cyclic AMP; D002118:Calcium; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside
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