Imagine trying to figure out how something works when something happens in a room less than a femtoliter: a quadrillionith of one liter. Now, two scientists with a nose to solve mysteries have used a combination of mathematical modeling, electrophysiology, and computer simulations to explain how cells communicate effectively in heavily narrowed spaces such as The olfactory cilia where odor detection takes place. The results will inform future studies of cellular signaling and communication in the olfactory system and also in other restricted spaces of the nervous system.
Study author Johannes Reisert, Ph.D., a cell physiologist from Monell Center, states: "Ion channels and how their amperage changes ion concentrations in cells are notoriously difficult to study. Our modeling approach allows us to better understand not only how olfaction works but also the function of small nerve endings such as dendrites, where pathology is associated with many neurodegenerative diseases. "
In the study published online prior to printing in Attempts by the National Academy of Sciences, the researchers asked why olfactory receptor cells communicate with the brain using a fundamentally different set of electrical events than those used by sensory cells in the visual or audio system.
Olfaction begins when an airborne chemical molecule in a process resembles a key that fits into a lock, moves through the nasal mucus to bind with an olfactory receptor embedded on the wall of a nerve cell in the nose. The olfactory receptors are located on cilia, elongated super-thin wire-like structures less than 0.000004 inches in diameter extending from the nerve cell into the mucosa.
The act of odor receptor binding initiates a complex molecular cascade within the olfactory cell, known as transduction, resulting in the nerve transmitting an electrical signal to illuminate the brain that an odor has been detected.
The transduction process culminates with the opening of pores called ion channels located in the nerve cell wall. The open pores allow positive or negative electrically charged molecules (ions) to flow in and out of the cell. This ultimately alters the cell's overall electrical charge to a less negative state, which is what initiates the cell's signal to the brain.
Most ion channels are selective for a specific ion, including positively charged sodium (Na+) ions or negatively charged chloride (Cl–). The flow of an ion through its channel in both directions generates an electric current.
Receptor cells in both the visual and auditory systems depend on inward flow of the ion currents to elicit an electrical signal. In contrast, the olfactory system is also dependent on outwardly flowing negative ion currents.
Using several approaches to developing a testable model of olfactory transduction and ionic currents, Reisert and his partner, computational neuroscience Jürgen Reingruber, Ph.D., from Ecole Normale Supérieure in Paris, could explain why the olfactory system works differently.
The researchers proved to rely on Cl– rather than Na+ As part of the transduction cascade provides several benefits that allow olfactory cells to respond more to odor more consistently.
One limitation facing the olfactory system is that the concentrations of Na+ and other positive ions in mucus outside the olfactory cells vary dramatically as a function of the nose's external environment. This makes it difficult for olfactory cells to depend on externally originating Na+ Streams as a reliable component of the transduction response.
The olfactory cells counteract this problem by using a C1– current originating from the cell, where the ionic concentrations are more stable, making Cl– current more reliable superiors.
"Imagine you have been swimming in the sea and your nose is bathed in salt water. This means that there is much more sodium outside the olfactory cells, but they must be able to function reliably if you have just swam in the sea or sitting in your kitchen, "said Reisert. "Replacement of externally original Na+ current with Cl– ions moving from within the cell to the outside solve that problem. "
The models also showed using the outgoing liquid Cl– ionic currents allow the olfactory cells to protect the infinitesimal intracellular space in the cilia, which is where ilfactic transduction occurs. This is because inward-flowing positive ions would encourage extra water to enter the space, potentially resulting in osmotic swelling and related structural damage to the cilia.
The results explain how the olfactory system can function reliably despite the challenging physical conditions in an unstable external environment and the small ciliary volume. An example of the fundamental value of basic science, this modeling method can now be used to investigate similar issues in other parts of the nervous system.
A new defender for your sense of smell
Ca2 + activated Cl stream provides robust and reliable signal amplification in vertebrate olfactory receptor neurons, Attempts by the National Academy of Sciences (2018). www.pnas.org/cgi/doi/10.1073/pnas.1816371116