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) alpha 1 and beta i n the development of hearing, cochlear functions have been investigated in mice lacking TR alpha 1 or TR beta. TRs are ligand-dependent transcription factors expressed in the developing organ of Corti, and loss of TR beta is known to impair hearing in mice and in humans. Here, TR alpha 1-deficient ( TR alpha 1(-/-)) mice are shown to display a normal auditory-evoked brainst em response, indicating that only TR beta, and not TR alpha 1, is essential for hearing. Because cochlear morphology was normal in TR beta(-/-) mice, we postulated that TR beta regulates functional rather than morphological d evelopment of the cochlea. At the onset of hearing, inner hair cells (IHCs) in wild-type mice express a fast-activating potassium conductance, I-K,I-f ,I- that transforms the immature MC from a regenerative, spiking pacemaker to a high-frequency signal transmitter. Expression of I-K,I-f was significa ntly retarded in TR beta(-/-) mice, whereas the development of the endococh lear potential and other cochlear functions, including mechano-electrical t ransduction in hair cells, progressed normally. TR alpha 1(-/-) mice expres sed I-K,I-f normally, in accord with their normal auditory evoked brainstem response. These results establish that the physiological differentiation o f IHCs depends on a TR beta-mediated pathway. When defective, this may cont ribute to deafness in congenital thyroid diseases.