Neuronal Chloride Accumulation in Olfactory Epithelium of Mice Lacking NKCC1

Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati, Cincinnati, Ohio Submitted 12 September 2005; accepted in final form 28 November 2005 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 Ca 2+ -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. Address for reprint requests and other correspondence: S. J. Kleene, Dept. of Cell Biology, Neurobiology, and Anatomy, Univ. of Cincinnati, PO Box 670667, Cincinnati, OH 45267-0667 (E-mail: steve{at}syrano.acb.uc.edu )