title: Neuronal chloride accumulation in olfactory epithelium of mice lacking NKCC1.
abstract: When stimulated with odorants, olfactory receptor neurons (ORNs) produce a depolarizing receptor current. In isolated ORNs, much of this current is caused by an efflux of Cl-. This implies that the neurons have one or more mechanisms for accumulating cytoplasmic Cl- at rest. Whether odors activate an efflux of Cl- in intact olfactory epithelium, where the ionic environment is poorly characterized, has not been previously determined. In mouse olfactory epithelium, we found that >80% of the summated electrical response to odors is blocked by niflumic acid or flufenamic acid, each of which inhibits Ca2+-activated Cl- channels in ORNs. This indicates that ORNs accumulate Cl- in situ. Recent evidence has shown that NKCC1, a Na+-K+-2Cl- cotransporter, contributes to Cl- accumulation in mammalian ORNs. However, we find that the epithelial response to odors is only reduced by 39% in mice carrying a null mutation in Nkcc1. As in the wild-type, most of the response is blocked by niflumic acid or flufenamic acid, indicating that the underlying current is carried by Cl-. We conclude that ORNs effectively accumulate Cl- in situ even in the absence of NKCC1. The Cl- -transport mechanism underlying this accumulation has not yet been identified.
authors.affiliation: Dept. of Cell Biology, Neurobiology, and Anatomy, Univ. of Cincinnati, PO Box 670667, Cincinnati, OH 45267-0667, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Nickell
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Kleene
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gesteland
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Kleene
mesh_terms: D000818:Animals; D002713:Chlorine / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology*; D051379:Mice; D009831:Olfactory Mucosa / Q000502:physiology*; D018034:Olfactory Receptor Neurons / Q000502:physiology*; D028021:Sodium-Potassium-Chloride Symporters / Q000172:deficiency*; D064506:Solute Carrier Family 12, Member 2
chemical_list: C578878:Slc12a2 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D002713:Chlorine