RESUMO
Recent observations regarding the non-selective action of outer hair cells contradict frequency-selective cochlear amplification. We hypothesized that active outer hair cells drive cochlear fluid circulation. The hypothesis was tested by delivering a neurotoxin, kainic acid, to the round window of young gerbil cochleae while monitoring auditory responses in the cochlear nucleus. Sounds presented at a modest level significantly expedited kainic acid delivery. When outer-hair-cell motility was suppressed by salicylate, the facilitation effect was compromised. A low-frequency tone was more effective than broadband noise, especially for drug delivery to apical locations. Computational model simulations provided the physical basis for our observation, which incorporated solute diffusion, fluid advection, fluid-structure interaction, and outer-hair-cell motility. Active outer hair cells deformed the organ of Corti like a peristaltic tube to generate apically streaming flows along the tunnel of Corti and basally streaming flows along the scala tympani. Our measurements and simulations coherently indicate that broadband outer-hair-cell action is for cochlear fluid circulation.
RESUMO
Peristaltic flows occur when fluid in a channel is driven by periodic, traveling wall deformations, as in industrial peristaltic pumps, urethras, stomachs, and cochleae. Peristaltic flows often vary periodically at every point in space but nonetheless cause net transport and mixing of solutes because of Lagrangian (Stokes) drift. Direct numerical simulation can predict peristaltic flows but is computationally expensive, particularly for determining functional relationships between drive parameters and transport or mixing. We present a simple analytic model of peristaltic flow that expresses flow velocity and drift velocity in terms of deformation speed and amplitude. The model extends beyond prior studies by allowing arbitrary wave forms via Fourier series. To validate our analytic model, we present experiments and simulations; both closely match the analytic model over a range of deformation speeds and amplitudes. We demonstrate the applicability of the model by quantifying variations in the thickness of the reflux region (where fluid drifts opposite the direction of travel of deformations) and by modeling mixing in the cochlea, which is promoted by peristaltic flow.
RESUMO
The cochlea is filled with two lymphatic fluids. Homeostasis of the cochlear fluids is essential for healthy hearing. The sensory epithelium called the organ of Corti separates the two fluids. Corti fluid space, extracellular fluid space within the organ of Corti, looks like a slender micro-tube. Substantial potassium ions are constantly released into the Corti fluid by sensory receptor cells. Excess potassium ions in the Corti fluid are resorbed by supporting cells to maintain fluid homeostasis. Through computational simulations, we investigated fluid mixing within the Corti fluid space. Two assumptions were made: first, there exists a longitudinal gradient of potassium ion concentration; second, outer hair cell motility causes organ of Corti deformations that alter the cross-sectional area of the Corti fluid space. We hypothesized that mechanical agitations can accelerate longitudinal mixing of Corti fluid. Corti fluid motion was determined by solving the Navier-Stokes equations incorporating nonlinear advection term. Advection-diffusion equation determined the mixing dynamics. Simulating traveling boundary waves, we found that advection and diffusion caused comparable mixing when the wave amplitude and speed were 25 nm and 7 m/s, respectively. Higher-amplitude and faster waves caused stronger advection. When physiological traveling waves corresponding to 70 dB sound pressure level at 9 kHz were simulated, advection speed was as large as 1 mm/s in the region basal to the peak responding location. Such physiological agitation accelerated longitudinal mixing by more than an order of magnitude, compared to pure diffusion. Our results suggest that fluid motion due to outer hair cell motility can help maintain longitudinal homeostasis of the Corti fluid.