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The Journal of Neuroscience, March 21, 2007, 27(12):3174-3186; doi:10.1523/JNEUROSCI.3965-06.2007

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Cellular/Molecular
Thyroid Hormone Deficiency Affects Postnatal Spiking Activity and Expression of Ca²⁺ and K⁺ Channels in Rodent Inner Hair Cells

Niels Brandt,^1 * Stephanie Kuhn,^1 * Stefan Münkner,¹ Claudia Braig,² Harald Winter,² Nikolaus Blin,³ Reinhard Vonthein,⁴ Marlies Knipper,² and Jutta Engel¹

¹Institute of Physiology II and Department of Otolaryngology, and ²Department of Otolaryngology, Molecular Neurobiology, Tübingen Hearing Research Centre, University of Tübingen, D-72076 Tübingen, Germany, ³Department of Molecular Genetics, Institute of Anthropology and Human Genetics, University of Tübingen, 72074 Tübingen, Germany, and ⁴Department of Medical Biometry, University of Tübingen, 72070 Tübingen, Germany

Correspondence should be addressed to Dr. Jutta Engel, University of Tübingen, Institute of Physiology II and Department of Otolaryngology, Tübingen Hearing Research Centre, Gmelinstrasse 5, D-72076 Tübingen, Germany. Email: jutta.engel{at}uni-tuebingen.de

Thyroid hormone (TH) is essential for the development of hearing. Lack of TH in a critical developmental period from embryonic day 17 to postnatal day 12 (P12) in rats and mice leads to morphological and functional deficits in the organ of Corti and the auditory pathway. We investigated the effects of TH on inner hair cells (IHCs) using patch-clamp recordings, capacitance measurements, and immunocytochemistry in hypothyroid rats and athyroid Pax8^–/– mice. Spontaneous and evoked Ca²⁺ action potentials (APs) were present in control IHCs from P3–P11 rats and vanished in parallel with the expression of a rapidly activating Ca²⁺- and voltage-activated K⁺ (BK) conductance. IHCs of hypothyroid rats and athyroid Pax8^–/– mice displayed APs until the end of the third postnatal week because of threefold elevated Ca²⁺ currents and missing expression of BK currents. After the fourth postnatal week, some IHCs showed BK currents whereas adjacent IHCs did not, demonstrated by electrophysiology and immunocytochemistry. To test whether the prolonged spiking activity during TH deficiency may be transmitted at IHC synapses, capacitance measurements were performed in parallel to analysis of otoferlin expression, a protein thought to play an essential role in exocytosis of IHCs. Strikingly, otoferlin was absent from IHCs of hypothyroid rats but not of Pax8^–/– mice, although both cell types showed exocytosis with an efficiency typical for immature IHCs. These results demonstrate for the first time a TH-dependent control of IHC spiking activity before the onset of hearing attributable to effects of TH on Ca²⁺ and BK channels. Moreover, they question an indispensable role of otoferlin for exocytosis in IHCs.

Key words: inner hair cell; thyroid hormone; BK channel; Ca_v1.3 channel; Ca²⁺ action potential; otoferlin

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Received Sept. 12, 2006; revised Feb. 20, 2007; accepted Feb. 21, 2007.

Correspondence should be addressed to Dr. Jutta Engel, University of Tübingen, Institute of Physiology II and Department of Otolaryngology, Tübingen Hearing Research Centre, Gmelinstrasse 5, D-72076 Tübingen, Germany. Email: jutta.engel{at}uni-tuebingen.de

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