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Mechanisms of neuronal chloride accumulation in intact mouse olfactory epithelium
Author(s) -
Nickell William T.,
Kleene Nancy K.,
Kleene Steven J.
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2007.129601
Subject(s) - bumetanide , cotransporter , olfactory epithelium , dids , chemistry , olfactory mucosa , transporter , receptor , microbiology and biotechnology , symporter , olfactory system , endocrinology , medicine , pharmacology , biochemistry , biophysics , biology , neuroscience , sodium , organic chemistry , membrane , gene
When olfactory receptor neurons respond to odours, a depolarizing Cl − efflux is a substantial part of the response. This requires that the resting neuron accumulate Cl − against an electrochemical gradient. In isolated olfactory receptor neurons, the Na + –K + –2Cl − cotransporter NKCC1 is essential for Cl − accumulation. However, in intact epithelium, a robust electrical olfactory response persists in mice lacking NKCC1. This response is largely due to a neuronal Cl − efflux. It thus appears that NKCC1 is an important part of a more complex system of Cl − accumulation. To identify the remaining transport proteins, we first screened by RT‐PCR for 21 Cl − transporters in mouse nasal tissue containing olfactory mucosa. For most of the Cl − transporters, the presence of mRNA was demonstrated. We also investigated the effects of pharmacological block or genetic ablation of Cl − transporters on the olfactory field potential, the electroolfactogram (EOG). Mice lacking the common Cl − /HCO 3 − exchanger AE2 had normal EOGs. Block of NKCC cotransport with bumetanide reduced the EOG in epithelia from wild‐type mice but had no effect in mice lacking NKCC1. Hydrochlorothiazide, a blocker of the Na + –Cl − cotransporter, had only a small effect. DIDS, a blocker of some KCC cotransporters and Cl − /HCO 3 − exchangers, reduced the EOG in epithelia from both wild‐type and NKCC1 knockout mice. A combination of bumetanide and DIDS decreased the response more than either drug alone. However, no combination of drugs completely abolished the Cl − component of the response. These results support the involvement of both NKCC1 and one or more DIDS‐sensitive transporters in Cl − accumulation in olfactory receptor neurons.