The coupling of acetylcholine-induced BK channel and calcium channel in guinea pig saccular type II vestibular hair cells
The coupling of acetylcholine-induced BK channel and calcium channel in guinea pig saccular type II vestibular hair cells
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DOI：
10.1016/j.brainres.2006.10.043
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发表时间：
2007-01-19
期刊：
影响因子：
2.9
通讯作者：
Van Cauwenberge, Paul
中科院分区：
文献类型：
--
作者：
Kong, Wen-Jia;Guo, Chang-Kai;Van Cauwenberge, Paul
分子生物学研究和电生理数据表明，乙酰胆碱（ACh）是耳蜗和前庭的主要传出神经递质。然而，乙酰胆碱在II型前庭毛细胞（VHCs II）中的功能作用尚不清楚，除了众所周知的α 9-含烟碱乙酰胆碱受体（α 9-含nAChR）激活的小电导，钙依赖性钾电流（SK）在耳蜗毛细胞和青蛙囊状毛细胞。SK电流的激活是钙通过含α 9的nAChR内流所必需的。近年来，我们发现豚鼠前庭终器VHC Ⅱ存在ACh诱导的大电导钙依赖性钾电流（BK）。本研究探讨了乙酰胆碱（ACh）激活豚鼠囊状VHCs II的BK电流时，钙内流的性质。ACh灌流后，囊状VHCs II显示持续的外向电流，对IBTX敏感。高浓度的apamin不能抑制ACh诱导的外向电流。胞内注射Cs+可完全阻断ACh诱发的电流。硝苯地平、尼莫地平、Cd ~（2+）和Ni ~（2+）均能有效地抑制ACh诱导的电流。4种钙拮抗剂的抑制作用大小依次为尼莫地平>硝苯地平>镉>镍。L-型钙通道激动剂Bay-K 8644模拟ACh的作用，激活IBTX敏感性电流。此外，部分VHC II显示双相波形。总之，目前的数据表明，在豚鼠囊状VHCs II，乙酰胆碱诱导的BK通道耦合的钙通道，但不是受体。ACh的灌注将驱动钙通道的开放;然后钙离子的流入将激活BK电流。(c)2006 Elsevier B. V.保留所有权利。
Molecular biological studies and electrophysiological data have demonstrated that acetylcholine (ACh) is the principal cochlear and vestibular efferent neurotransmitter among mammalians. However, the functional roles of ACh in type II vestibular hair cells (VHCs II) among mammalians are still unclear, with the exception of the well-known alpha 9-containing nicotinic ACh receptor (alpha 9-containing nAChR)-activated small conductance, calcium-dependent potassium current (SK) in cochlear hair cells and frog saccular hair cells. The activation of SK current was necessary for the calcium influx through the alpha 9-containing nAChR. Recently, we have demonstrated that ACh-induced big conductance, calcium-dependent potassium current (BK) was present in VHCs II of the vestibular end-organ of guinea pig. In this study, the nature of calcium influx for the activation of ACh-induced BK current in saccular VHCs II of guinea pig was investigated. Following extracellular perfusion of ACh, saccular VHCs II displayed a sustained outward current, which was sensitive to iberiotoxin (IBTX). High concentration of apamin failed to inhibit the current amplitude of ACh-induced outward current. Intracellular application of Cs+ completely abolished the current evoked by ACh. ACh-induced current was potently inhibited by nifedipine, nimodipine, Cd2+ and Ni2+, respectively. The inhibition potency of these four calcium channel antagonists was nimodipine > nifedipine > cadmium > nickel. The L-type Ca2+ channels agonist, (-)-Bay-K 8644 mimicked the effect of ACh and activated an IBTX-sensitive current. In addition, partial VHCs II displayed a biphasic waveform. In conclusion, the present data showed that in the guinea pig saccular VHCs II, ACh-induced BK channel was coupled with the calcium channel, but not the receptor. The perfusion of ACh will drive the opening of calcium channels; the influx of calcium ions will then activate the BK current. (c) 2006 Elsevier B.V. All rights reserved.