Thyroid hormone deficiency affects postnatal spiking activity and expression of Ca2+ and K+ channels in rodent inner hair cells.
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.
Brandt
Niels
N
Institute of Physiology II and Department of Otolaryngology, Tübingen Hearing Research Centre, University of Tübingen, D-72076 Tübingen, Germany.
Kuhn
Stephanie
S
Münkner
Stefan
S
Braig
Claudia
C
Winter
Harald
H
Blin
Nikolaus
N
Vonthein
Reinhard
R
Knipper
Marlies
M
Engel
Jutta
J
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006199:Hair Cells, Auditory, Inner / Q000254:growth & development / Q000378:metabolism*; D007037:Hypothyroidism / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D015221:Potassium Channels / Q000096:biosynthesis* / Q000235:genetics; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D015220:Calcium Channels; D015221:Potassium Channels