Disruption of Otoferlin Alters the Mode of Exocytosis at the Mouse Inner Hair Cell Ribbon Synapse

Sound encoding relies on Ca2+-mediated exocytosis at the ribbon synapse between cochlear inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs). Otoferlin, a multi-C2 domain protein, is proposed to regulate Ca2+-triggered exocytosis at this synapse, but the precise mechanisms of otoferlin function remain to be elucidated. Here, performing whole-cell voltage-clamp recordings of excitatory postsynaptic currents (EPSCs) from SGNs in otoferlin mutant mice, we investigated the impact of Otof disruption at individual synapses with single release event resolution. Otof deletion decreased the spontaneous release rate and abolished the stimulus-secretion coupling. This was evident from failure of potassium-induced IHC depolarization to stimulate release and supports the proposed role of otoferlin in Ca2+ sensing for fusion. A missense mutation in the Otof gene (pachanga), in which otoferlin level at the IHC plasma membrane was lowered without changing its Ca2+ binding, also reduced the spontaneous release rate but spared the stimulus-secretion coupling. The slowed stimulated release rate supports the hypothesis that a sufficient abundance of otoferlin at the plasma membrane is crucial for the vesicle supply. Large-sized monophasic EPSCs remained present upon Otof deletion despite the drastic reduction of the rate of exocytosis. However, EPSC amplitude, on average, was modestly decreased. Moreover, a reduced contribution of multiphasic EPSC was observed in both Otof mutants. We argue that the presence of large monophasic EPSCs despite the exocytic defect upon Otof deletion supports the uniquantal hypothesis of transmitter release at the IHC ribbon synapse. Based upon the reduced contribution of multiphasic EPSC, we propose a role of otoferlin in regulating the mode of exocytosis in IHCs

Hypothermic preservation of rat hearts using antifreeze glycoprotein

13301甲第5268号博士（医学）金沢大学博士論文本文Full 以下に掲載：PHYSIOLOGICAL RESEARCH 69 2020. ACAD SCIENCES CZECH REPUBLIC, INST PHYSIOLOGY. 共著者：Shintaro TAKAGO, Isao MATSUMOTO, Hiroki KATO, Naoki SAITO, Hideyasu, UEDA, Kenji IINO, Keiichi KIMURA, Hirofumi TAKEMUR

X線および中性子回折法によるFe-Cr/TiN系焼結複合材料の残留応力解析に関する研究

取得学位：博士(工学)，学位授与番号：博甲第385号，学位授与年月日：平成13年3月22日,学位授与年：200

X-ray elastic constant determination and residual stress estimation of spherical carbide in JIS SK3

After special surface treatments on specimens, residual stress behaviors of ferrite and cementite phases in two kind sizes of spheroidized JIS SK3 steels after tensile deformation were estimated by X-ray diffraction method. In the study, phase cementite X-ray elastic constant was obtained from composite X-ray elastic constants; compressive residual stresses were observed in ferrite and tensile residual stresses in cementite; the particle size of cementite has obvious affections on the residual stress behaviors of both cementite and ferrite; in order to well understand the interaction between cementite and matrix, the plastic strains of two phases and the misfit of plastic strain between them were analyzed based on Eshelby/Mori-Tanaka model. Copyright © 2006 by The International Society of Offshore and Polar Engineers

Disruption of Otoferlin Alters the Mode of Exocytosis at the Mouse Inner Hair Cell Ribbon Synapse

Sound encoding relies on Ca2+-mediated exocytosis at the ribbon synapse between cochlear inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs). Otoferlin, a multi-C-2 domain protein, is proposed to regulate Ca2+-triggered exocytosis at this synapse, but the precise mechanisms of otoferlin function remain to be elucidated. Here, performing whole-cell voltage-clamp recordings of excitatory postsynaptic currents (EPSCs) from SGNs in otoferlin mutant mice, we investigated the impact of Otof disruption at individual synapses with single release event resolution. Otof deletion decreased the spontaneous release rate and abolished the stimulus-secretion coupling. This was evident from failure of potassium-induced IHC depolarization to stimulate release and supports the proposed role of otoferlin in Ca2+ sensing for fusion. A missense mutation in the Otof gene (pachanga), in which otoferlin level at the IHC plasma membrane was lowered without changing its Ca2+ binding, also reduced the spontaneous release rate but spared the stimulus-secretion coupling. The slowed stimulated release rate supports the hypothesis that a sufficient abundance of otoferlin at the plasma membrane is crucial for the vesicle supply. Large-sized monophasic EPSCs remained present upon Otof deletion despite the drastic reduction of the rate of exocytosis. However, EPSC amplitude, on average, was modestly decreased. Moreover, a reduced contribution of multiphasic EPSC was observed in both Otof mutants. We argue that the presence of large monophasic EPSCs despite the exocytic defect upon Otof deletion supports the uniquantal hypothesis of transmitter release at the IHC ribbon synapse. Based upon the reduced contribution of multiphasic EPSC, we propose a role of otoferlin in regulating the mode of exocytosis in IHCs

Supporting data from NMDA receptor-dependent presynaptic inhibition at the calyx of Held synapse of rat pups

Raw data and statistical analyse