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首页> 外文期刊>The European Journal of Neuroscience >Ryanodine receptors and BK channels act as a presynaptic depressor of neurotransmission in cochlear inner hair cells.
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Ryanodine receptors and BK channels act as a presynaptic depressor of neurotransmission in cochlear inner hair cells.

机译:Ryanodine受体和BK通道在耳蜗内毛细胞中充当神经传递的突触前抑制物。

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Ryanodine receptors (RyRs) are known to contribute to the regulation of free cytosolic calcium concentration. This family of intracellular calcium channels plays a significant role in calcium-induced-calcium-release (CICR), and have been implicated in calcium-dependent processes requiring exquisite spatio-temporal regulation. In order to characterize the importance of these intracellular calcium channels in cochlear physiology, we perfused the guinea pig cochlea with antagonistic concentrations of ryanodine. The distortion products of the cochlear microphonic and the compound action potential of the auditory nerve were reversibly inhibited by ryanodine (IC(50) = 27.3 microm, Hill coefficient = 1.9), indicating an action at the cochlear amplifier. Single auditory nerve fibre recordings showed that ryanodine slightly increased spontaneous firing rates by 22%, suggesting an excitatory effect of ryanodine. This paradoxical effect could be explained by an inhibitory action of ryanodine on presynaptic BK channels of inner hair cells (IHC). Indeed, perfusing iberiotoxin also increased the spontaneous firing activity of the auditory nerve fibres. Furthermore, whole-cell patch-clamp recordings demonstrated that ryanodine inhibits BK currents at the IHC level. Conversely, immunohistochemistry demonstrated a strong expression of RyR in IHCs and, more particularly, below the cuticular plate where membranous BK channels are highly expressed. Overall, the study demonstrated a key role for RyR and CICR in signal transduction at the IHCs. We therefore propose that coupled RyR-BK channels act to suppress the fast neurotransmission in IHCs.
机译:已知Ryanodine受体(RyRs)有助于调节游离胞质钙的浓度。该家族的细胞内钙通道在钙诱导的钙释放(CICR)中起着重要作用,并与需要精确的时空调节的钙依赖性过程有关。为了表征这些细胞内钙通道在人工耳蜗生理中的重要性,我们向豚鼠耳蜗灌入了拮抗浓度的ryanodine。 ryanodine可逆地抑制了耳蜗微音的失真产物和听觉神经的复合动作电位(IC(50)= 27.3 microm,Hill系数= 1.9),表明在耳蜗放大器上有作用。单个听觉神经纤维录音显示,雷诺丁的自发放电率略有提高,提高了22%,表明了雷诺丁的兴奋作用。这种矛盾的作用可以通过ryanodine对内毛细胞(IHC)的突触前BK通道的抑制作用来解释。的确,灌输纤维毒素也增加了听神经纤维的自发放电活性。此外,全细胞膜片钳记录表明,ryanodine在IHC水平抑制了BK电流。相反,免疫组化显示了在IHC中RyR的强烈表达,尤其是在膜BK通道高度表达的表皮板下方。总体而言,该研究表明RyR和CICR在IHC的信号转导中起着关键作用。因此,我们建议耦合的RyR-BK通道可抑制IHC中的快速神经传递。

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