title: Ca2+ current-driven nonlinear amplification by the mammalian cochlea in vitro.
abstract: An active process in the inner ear expends energy to enhance the sensitivity and frequency selectivity of hearing. Two mechanisms have been proposed to underlie this process in the mammalian cochlea: receptor potential-based electromotility and Ca(2+)-driven active hair-bundle motility. To link the phenomenology of the cochlear amplifier with these cellular mechanisms, we developed an in vitro cochlear preparation from Meriones unguiculatus that affords optical access to the sensory epithelium while mimicking its in vivo environment. Acoustic and electrical stimulation elicited microphonic potentials and electrically evoked hair-bundle movement, demonstrating intact forward and reverse mechanotransduction. The mechanical responses of hair bundles from inner hair cells revealed a characteristic resonance and a compressive nonlinearity diagnostic of the active process. Blocking transduction with amiloride abolished nonlinear amplification, whereas eliminating all but the Ca(2+) component of the transduction current did not. These results suggest that the Ca(2+) current drives the cochlear active process, and they support the hypothesis that active hair-bundle motility underlies cochlear amplification.
authors.affiliation: Laboratory of Sensory Neuroscience and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
authors.forename: Dylan K
authors.initials: DK
authors.lastname: Chan
authors.forename: A J
authors.initials: AJ
authors.lastname: Hudspeth
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002923:Cilia / Q000502:physiology; D003051:Cochlea / Q000502:physiology*; D003055:Cochlear Microphonic Potentials / Q000187:drug effects / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004594:Electrophysiology; D004710:Endolymph / Q000187:drug effects; D005849:Gerbillinae; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000528:radiation effects; D008536:Meglumine / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology / Q000528:radiation effects; D017711:Nonlinear Dynamics; D011188:Potassium / Q000494:pharmacology
chemical_list: D008536:Meglumine; D000584:Amiloride; D011188:Potassium; D002118:Calcium