Imagine an attempt to figure out how something works when something happens in a space smaller than femtolithar: one quadrilithium per liter. Now, two scientists with a nose to solve mysteries used a combination of mathematical modeling, electrophysiology, and computer simulations to explain how cells effectively communicate in very cluttered spaces, such as olfactory germs, where smell is discovered. The findings will inform future studies on cellular signaling and communication in the olfactory system, as well as in other closed areas of the nervous system.
The author of the study, Dr. Johannes Reissert, a professor of cellular physiology from the Center of Monell, said: "The ion channels and how their currents change ionic concentrations in cells, are known to be hard to study. Our model-based approach enables us to better to 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 in advance on the printing in Proceedings of the National Academy of Sciences, scientists asked why olfactory receptor cells communicate with the brain using fundamentally different series of electrical events than they are used by sensory cells in visual or auditory systems.
Olfaction begins when, in a process similar to the key that fits in the lock, the chemical molecule in the air travels through the nasal mucus to bind to the olfactory receptor implanted on the wall of the nerve cell in the nose. Olfactory receptors are found on cilia, elongated super-thin structures with filaments smaller than 0.000004 inches in diameter, stretching from the nerve cell into the mucus.
The act of binding the odorant receptor initiates a complex molecular cascade inside the olfactory cell, known as transduction, resulting in the nerves sending an electrical signal to inform the brain that an odor has been detected.
The transduction process culminates with the opening of pores called ion channels, which are located in the wall of the nerve cells. Open pores allow cells to enter and exit positive or negative electrically charged molecules (ions). This eventually changes the total electrical charge of the cell to a less negative state, which is what initiates the signal of the cell 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 any direction generates an electric current.
The receptor cells both in the visual and auditory systems depend on the positive ion currents moving inside to generate an electrical signal. By contrast, the smelly system also relies on the outflows of negative ion currents.
Using multiple approaches to develop a model for the testing of olfactory transduction and ion currents, Reisert and his associate, computational neurologist Jürgen Renberger, a doctor at Ecole Normale Supérieure in Paris, could explain why the olfactory system works differently.
Researchers have shown that they rely on Cl– instead of the+ as part of the transduction cascade provides several advantages that enable the fragrant cells to respond to smells more consistently.
One limitation that confronts the olfactory system is that the concentrations of Na+ and other positive ions in the mucus outside the olfactory cells dramatically vary as a function of the external surrounding of the nose. This makes it difficult for olfactory cells to depend on Na-external origin+ currents as a reliable component of the transduction reaction.
Olfactory cells prevent this problem by using Cl– a stream originating from the cell's interior, where ion concentrations are more stable, making Cl– the current more secure.
"Imagine that you are swimming in the ocean and your nose is bathed in salty water, which means that there is much more sodium outside the olfactory cells, but they should be able to function reliably if you are swimming in the ocean or sitting in your kitchen, said Reiser. "Replacement of exterior originating Na+ current with Cl– ions that move from inside the cell to the outside solve that problem. "
The models also showed that the use of the outer flow of Cl– ion streams enable olfactory cells to protect the infinitesimal intracellular space of the ciliates, where olfactory transduction occurs. This is because positive ions moving from within will promote additional water to enter the space, which can potentially result in osmotic swelling and associated structural damage to the ciliary.
The results explain how the olfactory system is able to function depending on the challenging physical conditions of an unstable external environment and a small ciliary volume. An example of the powerful value of basic science, this modeling approach can now be used to examine similar issues in other parts of the nervous system.
New attorney for your sense of smell
The Ca2 + -activated Cl-current provides a stable and reliable amplification of the signal in the neurons of relief receptors of the vertebrates, Proceedings of the National Academy of Sciences (2018). www.pnas.org/cgi/doi/10.1073/pnas.1816371116