Purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular space
Purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular space
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DOI：
10.7554/elife.52160
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发表时间：
2020-01-08
期刊：
影响因子：
7.7
通讯作者：
Bergles, Dwight E.
中科院分区：
文献类型：
--
作者：
Babola, Travis A.;Kersbergen, Calvin J.;Bergles, Dwight E.
在发育中的感觉通路中的神经元表现出自发的电活动爆发，这对生存、成熟和电路完善至关重要。在听觉系统中，内在产生的活动发生在耳蜗处，但启动这种活动的分子机制仍然知之甚少。我们证明，小鼠内毛细胞在听力开始之前的爆发式放电需要由内支持细胞表达的P2RY1自身受体。P2RY1激活可引起毛细胞K+外流和去极化，以及支持细胞的渗透性收缩，从而显著增加细胞外空间和K+重新分配的速度。P2RY1的药物抑制或遗传干扰通过减少K+的释放来抑制神经元的爆发性放电，但意外地增强了神经元的紧张性放电，因为支持细胞的水再吸收减少了细胞外空间，导致K+积累。这些研究表明，支持细胞中的嘌呤能信号通过控制细胞外空间的体积来调节毛细胞的兴奋性。
Neurons in developing sensory pathways exhibit spontaneous bursts of electrical activity that are critical for survival, maturation and circuit refinement. In the auditory system, intrinsically generated activity arises within the cochlea, but the molecular mechanisms that initiate this activity remain poorly understood. We show that burst firing of mouse inner hair cells prior to hearing onset requires P2RY1 autoreceptors expressed by inner supporting cells. P2RY1 activation triggers K+ efflux and depolarization of hair cells, as well as osmotic shrinkage of supporting cells that dramatically increased the extracellular space and speed of K+ redistribution. Pharmacological inhibition or genetic disruption of P2RY1 suppressed neuronal burst firing by reducing K+ release, but unexpectedly enhanced their tonic firing, as water resorption by supporting cells reduced the extracellular space, leading to K+ accumulation. These studies indicate that purinergic signaling in supporting cells regulates hair cell excitability by controlling the volume of the extracellular space.