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三磷酸腺苷(ATP)抑制离体亨森氏细胞中的电压敏感性钾电流,硝苯地平可预防豚鼠噪声性听力损失。

Adenosine Triphosphate (ATP) Inhibits Voltage-Sensitive Potassium Currents in Isolated Hensen's Cells and Nifedipine Protects Against Noise-Induced Hearing Loss in Guinea Pigs.

作者信息

Ye Rui, Liu Jun, Jia Zhiying, Wang Hongyang, Wang YongAn, Sun Wei, Wu Xuan, Zhao Zhifei, Niu Baolong, Li Xingqi, Dai Guanghai, Li Jianxiong

机构信息

Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, China (mainland).

Department of Otolaryngology Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China (mainland).

出版信息

Med Sci Monit. 2016 Jun 13;22:2006-12. doi: 10.12659/msm.898150.

Abstract

BACKGROUND There is increasing evidence that adenosine triphosphate (ATP), a well-known neurotransmitter and neuromodulator in the central nervous system, plays an important role as an extracellular chemical messenger in the cochlea. MATERIAL AND METHODS Using a whole-cell recording technique, we studied the effects of ATP on isolated Hensen's cells, which are supporting cells in the cochlea, to determine if they are involved in the transduction of ions with hair cells. RESULTS ATP (0.1-10 µM) reduced the potassium current (IK+) in the majority of the recorded Hensen's cells (21 out of 25 cells). An inward current was also induced by high concentrations of ATP (100 µM to 10 mM), which was reversibly blocked by 100 µM suramin (a purinergic antagonist) and blocked by nifedipine (an L-type calcium channel blocker). After the cochleas were perfused with artificial perilymph solutions containing nifedipine and exposed to noise, the amplitude increase in the compound action potential (CAP) threshold and the reduction in cochlear microphonics was lower than when they were exposed to noise alone. CONCLUSIONS Our results suggest that ATP can block IK+ channels at a low concentration and induce an inward Ca2+ current at high concentrations, which is reversed by purinergic receptors. Nifedipine may have a partially protective effect on noise-induced hearing loss (NIHL).

摘要

背景

越来越多的证据表明,三磷酸腺苷(ATP)作为中枢神经系统中一种知名的神经递质和神经调质,在耳蜗中作为细胞外化学信使发挥着重要作用。

材料与方法

我们使用全细胞记录技术,研究了ATP对分离的亨森细胞(耳蜗中的支持细胞)的影响,以确定它们是否参与与毛细胞的离子转导。

结果

ATP(0.1 - 10 μM)降低了大多数记录的亨森细胞(25个细胞中的21个)中的钾电流(IK+)。高浓度的ATP(100 μM至10 mM)也诱导了内向电流,该电流被100 μM苏拉明(一种嘌呤能拮抗剂)可逆性阻断,并被硝苯地平(一种L型钙通道阻滞剂)阻断。在用含有硝苯地平的人工外淋巴溶液灌注耳蜗并暴露于噪声后,复合动作电位(CAP)阈值的幅度增加和耳蜗微音器电位的降低低于仅暴露于噪声时。

结论

我们的结果表明,ATP在低浓度时可阻断IK+通道,在高浓度时可诱导内向Ca2+电流,该电流可被嘌呤能受体逆转。硝苯地平可能对噪声性听力损失(NIHL)有部分保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c636/4913814/58fb951ed2ed/medscimonit-22-2006-g001.jpg

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