Synaptic organization in cochlear inner hair cells deficient for the CaV1.3 (α1D) subunit of L-type Ca2+ channels
Synaptic organization in cochlear inner hair cells deficient for the CaV1.3 (α1D) subunit of L-type Ca2+ channels
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DOI：
10.1016/j.neuroscience.2006.05.057
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Moser, T.
中科院分区：
文献类型：
--
作者：
Nemzou, R. M.;Bulankina, A. V.;Moser, T.
耳蜗内毛细胞（IHC）释放神经递质传入听觉神经纤维的声音刺激。内毛细胞的正常发育和功能需要形成L型电压门控Ca 2+通道（Ca（v）1.3）的亚基1.3的表达。我们使用免疫组织化学和反转录聚合酶链反应研究了缺乏Ca（v）1.3 Ca 2+通道（Ca（v）1.3（-/-））的小鼠的IHC中的突触组织和大电导Ca 2+激活钾通道的表达。)).尽管诱发传入突触传递几乎完全阻断，毛细胞带状突触形成，并保持保存至少4周后出生。此外，这些“沉默”的传入突触拥有突触机制的主要组成部分，如巴松管，短笛和CSP。因此，胞吐作用的阻断可能仅归因于缺乏通过Ca（v）1.3通道的Ca 2+内流。后来，Ca（v）1.3缺陷的IHC随后失去了它们的传入突触。这可能是由于继发性变性的突触后螺旋神经节neurons.In延长传出突触传递到Ca（v）1.3缺陷的IHC，这通常会在听力发作时停止，我们发现并列的免疫反应点传出突触前突触素和突触后（IHC）小电导钙激活钾通道（SK通道）出生后6周。最后，我们发现顶端耳蜗中大电导Ca 2+激活钾通道（BK）a亚基的mRNA大幅减少，这表明Ca（v）1.3缺陷型IHC中其基因的转录减少。Ca（v）1.3缺乏的毛细胞缺乏BK通道的顶端斑点样免疫反应性，而BK通道的顶端斑点样免疫反应性通常有助于毛细胞传入突触传递的时间精确性。综上所述，这些数据表明Ca（v）1.3通道在BK和SK通道表达的调节中起关键作用。Ca（v）1.3通道似乎不是带状突触形成所必需的，但对于维持带状突触和螺旋神经节神经元是必需的。(c)2006年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Cochlear inner hair cells (IHCs) release neurotransmitter onto afferent auditory nerve fibers in response to sound stimulation. Normal development and function of inner hair cells require the expression of a subunit 1.3 forming L-type voltage-gated Ca2+ channel (Ca(v)1.3).Here, we used immunohistochemistry and reverse transcri ption-polymerase chain reaction to study the synaptic organization and expression of large conductance Ca2+-activated potassium channels in IHCs of mice lacking the Ca(v)1.3 Ca2+ channel (Ca(v)1.3(-/-)). Despite the near complete block of evoked afferent synaptic transmission, hair cell ribbon synapses were formed and remained preserved for at least 4 weeks after birth. Moreover, these "silent" afferent synapses held major components of the synaptic machinery such as Bassoon, Piccolo, and CSP. Hence, the block of exocytosis might be solely attributed to the lack of Ca2+ influx through Ca(v)1.3 channels. Later on, Ca(v)1.3 deficient IHCs subsequently lost their afferent synapses. This was probably due to a secondary degeneration of the postsynaptic spiral ganglion neurons.In line with a prolonged efferent synaptic transmission onto Ca(v)1.3 deficient IHCs, which normally ceases around onset of hearing, we found juxtaposed immunoreactive spots of efferent presynaptic synaptophysin and postsynaptic (IHCs) small conductance Ca2+-activated potassium channels (SK channels) up to six weeks after birth. Finally, we show a substantial reduction of mRNA for the a subunit of the large conductance Ca2+-activated potassium channel (BK) in the apical cochlea, suggesting a reduced transcription of its gene in Ca(v)1.3 deficient IHCs. Ca(v)1.3 deficient IHCs lacked the apical spot-like immunoreactivity of clustered BK channels, which normally contribute to the temporal precision of hair cell afferent synaptic transmission.In summary, these data indicate that the Ca(v)1.3 channels are crucially involved in regulation of the expression of BK and SK channels. Ca(v)1.3 channels seem not to be essential for ribbon synapse formation, but are required for the maintenance of ribbon synapses and spiral ganglion neurons. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.