title: Thyroid hormone receptor beta-dependent expression of a potassium conductance in inner hair cells at the onset of hearing.
abstract: To elucidate the role of thyroid hormone receptors (TRs) alpha1 and beta in the development of hearing, cochlear functions have been investigated in mice lacking TRalpha1 or TRbeta. TRs are ligand-dependent transcription factors expressed in the developing organ of Corti, and loss of TRbeta is known to impair hearing in mice and in humans. Here, TRalpha1-deficient (TRalpha1(-/-)) mice are shown to display a normal auditory-evoked brainstem response, indicating that only TRbeta, and not TRalpha1, is essential for hearing. Because cochlear morphology was normal in TRbeta-/- mice, we postulated that TRbeta regulates functional rather than morphological development of the cochlea. At the onset of hearing, inner hair cells (IHCs) in wild-type mice express a fast-activating potassium conductance, IK,f, that transforms the immature IHC from a regenerative, spiking pacemaker to a high-frequency signal transmitter. Expression of IK,f was significantly retarded in TRbeta-/- mice, whereas the development of the endocochlear potential and other cochlear functions, including mechanoelectrical transduction in hair cells, progressed normally. TRalpha1(-/-) mice expressed IK,f normally, in accord with their normal auditory-evoked brainstem response. These results establish that the physiological differentiation of IHCs depends on a TRbeta-mediated pathway. When defective, this may contribute to deafness in congenital thyroid diseases.
authors.affiliation: Physiologisches Institut, Gmelinstrasse 5, and Sektion Sensorische Biophysik, Hals-Nasen-Ohren Klinik, Röntgenweg 11, Universität T ubingen, D-72076 Tübingen, Germany. alfons.ruesch@uni-tuebingen.de
authors.forename: A
authors.initials: A
authors.lastname: Rüsch
authors.forename: L C
authors.initials: LC
authors.lastname: Erway
authors.forename: D
authors.initials: D
authors.lastname: Oliver
authors.forename: B
authors.initials: B
authors.lastname: Vennström
authors.forename: D
authors.initials: D
authors.lastname: Forrest
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D003051:Cochlea / Q000254:growth & development / Q000502:physiology; D016057:Evoked Potentials, Auditory, Brain Stem; D005786:Gene Expression Regulation; D006199:Hair Cells, Auditory, Inner / Q000502:physiology*; D006309:Hearing / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009925:Organ of Corti / Q000502:physiology; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology; D011988:Receptors, Thyroid Hormone / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D015221:Potassium Channels; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors