Nanoscale mathematical modeling of synaptic transmission, calcium dynamics, transduction and cell sensing

# course: Sensory transduction in vertebrate olfactory receptor neurons

speaker: Jürgen Reingruber (ENS, Paris)

abstract: The activation of odorant receptors located in the cilia of vertebrate olfactory receptor neurons (ORNs) initiates a signal transduction current that is largely carried by $Ca{2+}$-activated $Cl-$ channels (Anoctamin 2, Ano2). However, neither the functional role of the $Cl-$ current that can carry several hundred pA is fully understood, nor is it clear why the depolarizing current is anionic and not cationic as in photoreceptors, for example. Here we provide a putative explanation for the latter by studying the impact of a transduction current that is carried either by $Cl-$ or $Na+$ on the ion dynamics in the constrained and small space of olfactory cilia. To carry out the analysis we developed a spatio-temporal model that takes into account the coupled dynamics of $Na+$, $Ca{2+}$, $K+$ and $Cl-$. We validated the model using experimental data and performed simulations to compare the consequences of an odorant response based on either a $Cl-$ or $Na+$ current. Our main findings are: First, contrary to a $Cl-$ current, a $Na+$ current induces a large increase in the ciliary $Na+$ concentration during the odorant response. Second, contrary to a $Na+$ current, a transduction pathway based on a $Cl-$ current is robust and little affected by external $Cl-$ or $Na+$ concentration changes in the mucus. Third, a $Na+$ current can increase the ciliary $Na+$ concentration to a level where the $Na+Ca{2+}K+$ exchanger mode is reversed and odorant response termination is compromised. In reverse mode the exchanger transports $Ca{2+}$ into the cilia, which can sustain the $Ca{2+}$-activated current even in absence of odorant stimulation. Fourth, contrary to a $Cl-$ current, a $Na+$ current increases osmotic concentration and pressure in cilia during the odorant response, which might compromise the mechanical stability of fragile cilia because of potential water influx.

timetable:
Fri 12 Oct, 12:00 - 13:00, Aula Dini
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