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Adenophostin A and imipramine are two activators of the olfactory inositol 1,4,5-trisphosphate-gated channel in fish olfatory cilia

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Abstract

Binding of an odorant to its receptor activates the cAMP-dependent pathway, and also leads to inositol 1,4,5-trisphosphate (InsP3) production. This induces opening of a plasma membrane channel in olfactory receptor cells (ORCs). We investigated single-channel properties of this channel in the presence of a phospholipase C (PLC) activator (imipramine) and of a potent activator of the InsP3/Ca2+ release channel (adenophostin A) by reconstituting carp olfactory cilia into planar lipid bilayers. In the presence of 53 mM barium as a charge carrier, the addition of 50 µM imipramine induced a current of 1.53±0.05 pA at 0 mV. There were two different mean open times (6.0±0.6 ms and 49.6±6.4 ms). The I/V curve displayed a slope conductance of 50±2 pS. Channel activity was transient and was blocked by neomycin (50 µM). These observations suggest that imipramine may activate the olfactory InsP3-gated channel through PLC. Using the same ionic conditions, the application of 0.5 µM adenophostin A triggered a current of 1.47±0.04 pA at 0 mV. The I/V curve displayed a slope conductance of 60±2 pS. This channel showed only a single mean open time (15.0±0.3 ms) and was strongly inhibited by ruthenium red (30 µM) and heparin (10 µg/mL). These results indicate that adenophostin A and imipramine may act on the ciliary InsP3-gated channel and are potentially valuable pharmacological tools for studying olfactory transduction mechanisms.

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Fig. 1A–D.
Fig. 2A, B.
Fig. 3A–D.
Fig. 4A, B.

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Abbreviations

CNGc :

cyclic nucleotide-gated channel

EDTA :

ethylenediaminetetraacetic acid

EGTA :

ethyleneglycol-bis(β-aminoethyl)-N,N,N',N'-tetraacetic acid

ER :

endoplasmic reticulum

HEEDTA :

N-(2-hydroxyethyl)ethylenediaminetriacetic acid

HEPES :

N-2-(hydroxyethyl)piperazine-N'-(2-ethanesulfonic acid)

InsP 3 :

inositol 1,4,5-trisphosphate

ORCs :

olfactory receptor cells

PdtIns(4,5)P 2 :

phosphatidylinositol 4,5-bisphosphate

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Acknowledgements

This work was supported by a grant from the Région Haute Normandie (HC). The authors wish to thank Dr. Frank Wissing (University of Heidelberg) for suggestions in the use of adenophostin A and for reviewing an earlier version of this manuscript.

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Authors and Affiliations

  1. Centre de Biochimie Structurale, UMR 5048 CNRS, 554 INSERM, 29 rue de Navacelles, 34090 , Montpellier, France

    Gérard Molle

  2. UMR 6522 CNRS, IFRMP 23, Université de Rouen, 76821 , Mont-Saint-Aignan, France

    Hervé Cadiou

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  1. Hervé Cadiou
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  2. Gérard Molle
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Correspondence to Gérard Molle.

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Cadiou, H., Molle, G. Adenophostin A and imipramine are two activators of the olfactory inositol 1,4,5-trisphosphate-gated channel in fish olfatory cilia. Eur Biophys J 32, 106–112 (2003). https://doi.org/10.1007/s00249-002-0271-x

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