Artikel
Maturation of hair cell synaptic coding is driven by thyroid hormone
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Veröffentlicht: | 24. April 2007 |
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Gliederung
Text
Ribbon synapses of inner hair cells (IHCs) undergo developmental maturation until after the onset of hearing. Here, we studied whether IHC synaptogenesis is regulated by thyroid hormone (TH).
We performed perforated patch-clamp recordings of Ca2+ currents and exocytic membrane capacitance changes in IHCs of athyroid Pax8-/- mice during development. Like in wild-type (wt) IHCs, large Ca2+ currents were present in IHCs of Pax8-/- mice at the end of the first postnatal week. Different from wt, their Ca2+ currents remained elevated when tested at postnatal day 15, which then elicited robust exocytosis, albeit with reduced efficiency. Ribbon synapses were formed despite the TH-deficiency. However, different from wt, where synapse elimination takes place around the onset of hearing, the number of ribbon synapses remained elevated in 2-week-old Pax8-/- IHCs. Moreover, the ultrastructure of these synapses appeared immature. Using quantitative RT-PCR we found a TH-dependent developmental upregulation of the mRNAs for the neuronal SNARE proteins SNAP25 and synaptobrevin 1 in the organ of Corti. These molecular changes probably contribute to the improvement of exocytosis efficiency in mature IHCs. IHCs of 2-week-old Pax8-/- mice maintained the normally temporary efferent innervation further indicating an impaired postnatal IHC development. Moreover, they lacked functional large conductance Ca2+ activated K+ channels and KCNQ4 channels and consequently fired action potentials.
We conclude that TH regulates IHC differentiation and is essential for morphological and functional maturation of their ribbon synapses. We suggest that presynaptic dysfunction of IHCs is a mechanism in congenital hypothyroid deafness.
Supported by: EC (Eurohear), HFSPO, DFG