title: Underestimated sensitivity of mammalian cochlear hair cells due to splay between stereociliary columns.
abstract: Current-displacement (I-X) and the force-displacement (F-X) relationships characterize hair-cell mechano-transduction in the inner ear. A common technique for measuring these relationships is to deliver mechanical stimulations to individual hair bundles with microprobes and measure whole cell transduction currents through patch pipette electrodes at the basolateral membrane. The sensitivity of hair-cell mechano-transduction is determined by two fundamental biophysical properties of the mechano-transduction channel, the stiffness of the putative gating spring and the gating swing, which are derived from the I-X and F-X relationships. Although the hair-cell stereocilia in vivo deflect <100 nm even at high sound pressure levels, often it takes >500 nm of stereocilia displacement to saturate hair-cell mechano-transduction in experiments with individual hair cells in vitro. Despite such discrepancy between in vivo and in vitro data, key biophysical properties of hair-cell mechano-transduction to define the transduction sensitivity have been estimated from in vitro experiments. Using three-dimensional finite-element methods, we modeled an inner hair-cell and an outer hair-cell stereocilia bundle and simulated the effect of probe stimulation. Unlike the natural situation where the tectorial membrane stimulates hair-cell stereocilia evenly, probes deflect stereocilia unevenly. Because of uneven stimulation, 1) the operating range (the 10-90% width of the I-X relationship) increases by a factor of 2-8 depending on probe shapes, 2) the I-X relationship changes from a symmetric to an asymmetric function, and 3) the bundle stiffness is underestimated. Our results indicate that the generally accepted assumption of parallel stimulation leads to an overestimation of the gating swing and underestimation of the gating spring stiffness by an order of magnitude.
authors.affiliation: Department of Mechanical Engineering, University of Rochester, Rochester, New York; Department of Biomedical Engineering, University of Rochester, Rochester, New York. Electronic address: jong-hoon.nam@rochester.edu.
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Nam
authors.affiliation: Department of Otolaryngology, Stanford University School of Medicine, Stanford, California.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Peng
authors.affiliation: Department of Otolaryngology, Stanford University School of Medicine, Stanford, California; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Ricci
mesh_terms: D000818:Animals; D016477:Artifacts; D001696:Biomechanical Phenomena; D055724:Electrophysiological Phenomena; D020342:Finite Element Analysis; D006199:Hair Cells, Auditory, Inner / Q000166:cytology*; D018072:Hair Cells, Auditory, Outer / Q000166:cytology*; D040542:Mechanotransduction, Cellular; D008853:Microscopy; D008954:Models, Biological; D051381:Rats; D059547:Stereocilia / Q000378:metabolism*