The Styryl Dye FM1-43 Suppresses Odorant Responses in a Subset of Olfactory Neurons by Blocking Cyclic Nucleotide-gated (CNG) Channels
Esther Breunig, Eugen Kludt, Dirk Czesnik, Detlev Schild
Abstract
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Esther Breunig, Eugen Kludt, Dirk Czesnik, Detlev Schild
Abstract
Open-access reader
Many olfactory receptor neurons use a cAMP-dependent transduction mechanism to transduce odorants into depolarizations. This signaling cascade is characterized by a sequence of two currents: a cation current through cyclic nucleotide-gated channels followed by a chloride current through calcium-activated chloride channels. To date, it is not possible to interfere with these generator channels under physiological conditions with potent and specific blockers. In this study we identified the styryl dye FM1-43 as a potent blocker of native olfactory cyclic nucleotide-gated channels. Furthermore, we characterized this substance to stain olfactory receptor neurons that are endowed with cAMP-dependent transduction. This allows optical differentiation and pharmacological interference with olfactory receptor neurons at the level of the signal transduction.
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Many olfactory receptor neurons use a cAMP-dependent transduction mechanism to transduce odorants into depolarizations. This signaling cascade is characterized by a sequence of two currents: a cation current through cyclic nucleotide-gated channels followed by a chloride current through calcium-activated chloride channels. To date, it is not possible to interfere with these generator channels under physiological conditions with potent and specific blockers. In this study we identified the styryl dye FM1-43 as a potent blocker of native olfactory cyclic nucleotide-gated channels. Furthermore, we characterized this substance to stain olfactory receptor neurons that are endowed with cAMP-dependent transduction. This allows optical differentiation and pharmacological interference with olfactory receptor neurons at the level of the signal transduction.
Key concepts: Cyclic nucleotide-gated ion channel, Olfactory receptor, Transduction (biophysics), Cyclic nucleotide, Chemistry, Signal transduction, Olfactory system, Chloride channel