Archive

Deiters’ cells are important supporting cells of the sensory receptor cells in the organ of Corti. They provide a physical and metabolic support to the outer hair cells, modulate their electromotility and contribute to the cochlear amplification of the sound. However, their role and their mechanism of action are not completely understood. The purpose of developing a deeper understanding of the Deiters’ cells’ functions and properties is believed to have an interest in pharmacological and therapeutical treatments. It could help improve hearing and develop a possible treatment for hearing impairment. To this context, Ca2+ signalling pathways in Deiters’ cells are studied to provide insight into the regulation of their intracellular processes and intercellular communication.

The cochlea, in which the organ of Corti lies, has a characteristic snail shape. It can be divided into three cochlear turns : apical, middle and basal turns. In mice, the most commonly used animal models in hearing research, the cochlea has a complex morphology and size making its cells difficult to study. Thus, mathematical models would be a valuable tool for the study of Deiters’ cells of the different cochlear turns.

This study aimed at developing a mathematical model to simulate ATP-evoked Ca2+ signalling and Ca2+-induced gap junctional opening and closing mechanisms in Deiters’ cells. The model was compared with data obtained from a Ca2+ imaging experiment performed previously to demonstrate Deiters’ cells’ Ca2+ activity. The model was based on Taheri et al. (2017) and De Pittà et al. (2009) models. ATP stimuli were treated as inputs to the model. Besides, Wu et al. (2004) model was used to describe gap junctional IP3 diffusion from neighboring cells. Indeed, carbenoxolone was experimentally used to investigate gap junctional coupling mechanisms in Deiters’ cells. Although it was consider to block the connexin channels non-selectively, it is also thought to block other pathways such as the IP3R pathway. Both hypotheses were tested with our model.

Over 300,000 model parameter values were tested in order to successfully model ATP-induced Ca2+ transients in the apical and middle turns of the organ of Corti. Our model fits with the experimental results. Furthermore, it may provide a better understanding of the mechanism of action of carbenoxolone and the importance of gap junctions in Deiters’ cells.