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Presentations

• Nam, J-H. & Fettiplace, R. 2010. Organ of Corti Micromachine Enables Hair Bundles to Deform Basilar Membrane 3 MB Presented at the , San Francisco, CA.

  Abstract

  The Organ of Corti (OC) is a highly organized structure in the mammalian cochlea that houses the sensory hair cells. It is believed that the OC functions to optimize force transmission from the outer hair cell (OHC) to the basilar membrane and the inner hair cell. Recent studies reveal that the OC cannot be considered as a rigid body and has a complex mode of deformation. We developed a 3-D finite element model of the OC to dissect its mechanics. Geometric and mechanical information was taken from the gerbil cochlea at 2 and 10 mm from the stapes, positions encoding high and low frequencies respectively, and in each case several hundred microns longitudinal extent was simulated. The model included all structurally significant components: OHCs, pillar cells, Deiters cells and reticular lamina. The model was validated by reproducing experimental results on point stiffness and longitudinal space constant measured at the basilar membrane and response to current steps through the OC. Deformation of the OC by two different active OHC forces (the OHC somatic force and the stereociliary-based force) was then simulated. A surprising result was that despite smaller magnitude, the stereociliary-based force (0.1and 0.7 nN at apex and base) was nearly as effective as the somatic force (10 nN) in displacing the basilar membrane. The results also suggested that for the active forces to work efficiently the radial stiffness of the tectorial membrane must be comparable to or greater than the hair bundle stiffness. Funded by NIH RO1 DC01362.

• Nam, J-H., Beurg, M., Hackney, C. & Fettiplace, R. 2009. Calcium Dynamics in the Stereociliary Bundle of Rat Cochlear Hair Cells 2 MB Presented at the , Boston, MA.

  Abstract

  The stereociliary bundle on top of the cochlear hair cell converts the mechanical stimuli into an electric signal by opening of mechanotransducer (MT) channels that are both highly permeable to and regulated by calcium. Calcium dynamics in the apical region of the hair cell was recorded by fast imaging of the fluorescent dye Fluo-4FF with temporal and spatial resolutions of 2 ms and 0.1 µm. This resolution enabled capture and localization of fast calcium transients in stereocilia of diameter 0.25-0.5 µm. The results were simulated with a computer model incorporating calcium influx through MT channels, binding to mobile and fixed calcium buffers, uptake into mitochondria and extrusion by CaATPase pumps. The transient calcium profile within 100 ms was dominated by the mobile and fixed buffers rather than PMCA pumps and mitochondria. Experimental results agreed with the simulation when there was at least 1 mM of fixed buffer with dissociation coefficient greater than 10 µM. High affinity mobile buffer had the greatest effect on the peak calcium at the stereociliary tips. With 2000 and 200 calcium pumps/µm² in the stereociliary bundle and cell body respectively, the hair cell could cope with a resting calcium current up to 15 pA, 10 per cent of the maximal calcium current in vitro. Blocking the CaATPase or mitochondrial uniporter raised the somatic calcium level and slowed the calcium decay after a stimulus, agreeing with the experimental results. Data showed that when MT channels were open, the calcium concentration decayed from tip to rootlet in the two rows of short stereocilia but increased in the tallest stereocilia. This result was best reproduced if there were MT channels in the two shorter stereocilia but none in the tallest stereocilia. Supported by NIH RO1 DC03896.