Thyroid hormone receptor beta-dependent expression of a potassium conductance in inner hair cells at the onset of hearing.
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.
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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
Erway
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Oliver
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Vennström
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Forrest
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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*
D015221:Potassium Channels; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors