Adenophostin A and imipramine are two activators of the olfactory inositol 1,4,5-trisphosphate-gated channel in fish olfatory cilia.
Binding of an odorant to its receptor activates the cAMP-dependent pathway, and also leads to inositol 1,4,5-trisphosphate (InsP(3)) 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 InsP(3)/Ca(2+) 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 microM 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 microM). These observations suggest that imipramine may activate the olfactory InsP(3)-gated channel through PLC. Using the same ionic conditions, the application of 0.5 microM 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 microM) and heparin (10 microg/mL). These results indicate that adenophostin A and imipramine may act on the ciliary InsP(3)-gated channel and are potentially valuable pharmacological tools for studying olfactory transduction mechanisms.
UMR 6522 CNRS, IFRMP 23, Université de Rouen, 76821 Mont-Saint-Aignan, France.
Hervé
H
Cadiou
Gérard
G
Molle
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D002347:Carps; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D007099:Imipramine / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008051:Lipid Bilayers / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009297:Nasal Mucosa / Q000187:drug effects / Q000502:physiology*; D018034:Olfactory Receptor Neurons / Q000502:physiology; D010738:Type C Phospholipases / Q000187:drug effects / Q000378:metabolism
D007473:Ion Channels; D008051:Lipid Bilayers; C085029:adenophostin A; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D000241:Adenosine; D007099:Imipramine