# The roles and functions of olfactory transduction channels in the odorant response

> **NIH NIH R01** · MONELL CHEMICAL SENSES CENTER · 2020 · $349,068

## Abstract

Summary
 Our senses convert environmental stimuli into electrical signals that are ultimately interpreted by the brain
to guide our behavioral decisions. The conversion of stimuli relies on the ion channels expressed in sensory
cells, and their properties thus determine how we perceive our environment. Olfactory receptor neurons
(ORNs) in the nasal cavity recognize odorants and, unlike other sensory neurons such as photoreceptors and
hair cells, are in direct contact with the external environment, protected only by a thin mucus layer. Olfactory
cilia, the cellular compartment that contains the machinery that transduces odorants, must survive in this
environment while remaining functional, adding extra demands on membrane integrity and function.
 The initial event of an odor molecule binding to an odorant receptor in the ciliary membrane leads, via
activation of adenylyl cyclase, to opening of the olfactory cyclic-nucleotide gated (CNG) channel that allows
Ca2+ influx, which in turn activates an excitatory Ca2+-activated Cl- channel, further depolarizing the neuron.
This two-tiered sensory transduction mechanism based on one cationic and one anionic channels, is unique to
ORNs and highly conserved across all vertebrates. Both the reason why ORNs use this two-stage ion channel
system in general and why a combination of cation and anion conductances in particular is used to perceive
odorants are unclear, as is the role of the Ca2+-activated Cl- channel.
 Only in 2009 was the molecular identity of the olfactory Ca2+-activated Cl- channel determined to be
anoctamin 2 (Ano2), and despite a knockout model being available, the roles of Ano2, and therefore also of the
CNG channel, remain unclear. We propose to use an Ano2-knockout mouse, electrophysiological and
molecular approaches to define how these two ion channels shape the odorant-induced response. We will
characterize which specific aspects of the response (adaptation, response reliability, action potential coding,
etc.) are determined by a single ion channel or jointly by both. In addition, because the two channels must
function in the constraints of the ciliary membrane, we will investigate how the channels rely on membrane
constituents for their function and how altered membranes leads to detrimental olfactory function.
 By examining how the two-tiered sensory transduction mechanism of a cationic and an anionic ion
channel operates seamlessly as a dual-component system, we will address fundamental questions in olfaction
that have remained unanswered for the past 25 years.
 The long-term goal of this proposal is to establish how ORNs use their signal transduction in general and
their ion channels in particular to reliably encode odorant stimuli, how transduction functions within the
constraints of the ciliary membrane, and how this ultimately determines how odorants are perceived.

## Key facts

- **NIH application ID:** 9948632
- **Project number:** 5R01DC016647-03
- **Recipient organization:** MONELL CHEMICAL SENSES CENTER
- **Principal Investigator:** JOHANNES REISERT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $349,068
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948632

## Citation

> US National Institutes of Health, RePORTER application 9948632, The roles and functions of olfactory transduction channels in the odorant response (5R01DC016647-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9948632. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*