Tonotopic variation in the calcium dependence of neurotransmitter release and vesicle pool replenishment at mammalian auditory ribbon synapses.
Tonotopic variation in the calcium dependence of neurotransmitter release and vesicle pool replenishment at mammalian auditory ribbon synapses.
复制标题
神经递质释放的钙依赖性和囊泡池补充的钙依赖性变化。
DOI：
10.1523/jneurosci.0785-08.2008
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发表时间：
2008-07-23
期刊：
影响因子：
--
通讯作者：
Marcotti W
中科院分区：
文献类型：
--
作者：
Johnson SL;Forge A;Knipper M;Münkner S;Marcotti W
哺乳动物的耳蜗专门识别和处理复杂的听觉信号，在很宽的频率范围内具有显著的灵敏度和时间精度。传递到听觉传入纤维的信息质量主要取决于内毛细胞（IHC）带状突触的传递特性。为了研究突触机制的生物物理特性，我们测量了在接近生理条件（1.3 mm细胞外Ca2+和体温）下维持的沙鼠ihc的低频（顶端区域，~ 300 Hz）和高频（基部，~ 30 kHz）膜电容的变化（ΔCm）。随着成熟，Ca2+的胞外分泌效率在顶端和基部的IHCs中都有所提高，后者更为明显。听力前的IHCs表现出类似的Ca2+胞外协同作用，尽管在顶端细胞中ΔCm较小。成熟后，高频ihc中的ΔCm随Ca2+电流线性增加，然而，令人惊讶的是，低频细胞中的关系明显更加非线性。这种张力异位差异似乎与带状突触形态（顶端为球形，基部为椭圆体）有关，但与钙离子传感器otoferlin的表达水平或钙离子通道与活性区之间的空间耦合无关。成人ihc的重复刺激表明，囊泡池再填充可能成为囊泡释放的速率限制，高频ihc能够维持更高的释放速率。总之，我们的发现为哺乳动物间充质干细胞突触机制特性的张力异位差异提供了第一个证据，这可能是在声音刺激下微调其受体特性所必需的。
The mammalian cochlea is specialized to recognize and process complex auditory signals with remarkable acuity and temporal precision over a wide frequency range. The quality of the information relayed to the auditory afferent fibers mainly depends on the transfer characteristics of inner hair cell (IHC) ribbon synapses. To investigate the biophysical properties of the synaptic machinery, we measured changes in membrane capacitance (ΔCm) in low-frequency (apical region, ∼300 Hz) and high-frequency (basal, ∼30 kHz) gerbil IHCs maintained in near physiological conditions (1.3 mm extracellular Ca2+ and body temperature). With maturation, the Ca2+ efficiency of exocytosis improved in both apical and basal IHCs and was more pronounced in the latter. Prehearing IHCs showed a similar Ca2+ cooperativity of exocytosis despite the smaller ΔCm in apical cells. After maturation, ΔCm in high-frequency IHCs increased linearly with the Ca2+ current, whereas, somewhat surprisingly, the relationship was significantly more nonlinear in low-frequency cells. This tonotopic difference seemed to be correlated with ribbon synapse morphology (spherical in apical and ellipsoid in basal IHCs) but not with the expression level of the proposed Ca2+ sensor otoferlin or the spatial coupling between Ca2+ channels and active zones. Repetitive stimulation of adult IHCs showed that vesicle pool refilling could become rate limiting for vesicle release, with high-frequency IHCs able to sustain greater release rates. Together, our findings provide the first evidence for a tonotopic difference in the properties of the synaptic machinery in mammalian IHCs, which could be essential for fine-tuning their receptor characteristics during sound stimulation.