50. 3D current flow in a large scale model of the cochlea and the effect of mutations on sound transduction

P. Mistrik p.mistrik@ucl.ac.uk J. Ashmore j.ashmore@ucl.ac.uk

Ear Institute and Division of Neuroscience, Physiology and Pharmacology, UCL, London, UK

Sound perception is facilitated by mechano-electrical transduction in the hair cells, sensory cells of the cochlea of the inner ear. The transduction is brought about by the sound-induced potassium influx, which induces changes in membrane potential facilitating neuronal encoding of incoming sound.

Here we present a large scale computational model of potassium circulation in the cochlea. The cochlea is in the model split longitudinally into 300 sections and each section divided into 6 compartments (scala media, inner hair cell (IHC), outer hair cell (OHC), extracellular space near IHCs, extracellular space near OHCs and stria vascularis). This semi-cellular network is described as an equivalent three-dimensional electrical circuit of resistors, capacitors and batteries and the flow of potassium ions is treated as electrical current. The sound-induced potassium influx into hair cells is represented by variable resistors realistically reflecting the cochlear macromechanics. The MATLAB simulations describe the dependence of the electrical potentials of hair cells, governing sensitivity and frequency selectivity of transduction process, on the frequency of sound.

As the model is based on the molecular potassium circuits in the cochlea it allows the assessment of how do mutations in the potassium-transport related genes affect the electrical properties of hair cells and thus the sound transduction. The model was used to analyse the role of mutations in gap junctions, the most common cause of deafness, and potassium transporters, also known to be involved in some hearing impairments. The simulations indicate that reduced conductivity due to these mutations decreases the hair cells electrical potentials at high frequencies, compromising the sensitivity and frequency selectivity. Thus, gap junctions related forms of deafness can be explained by a decreased recirculation of potassium ions in the cochlea. This computational-based approach could serve as in silico platform for understanding the effect of gene mutations on the function of the cochlea.