M2 muscarinic ACh receptors sensitive BK channels mediate cholinergic inhibition of type II vestibular hair cells
- 作者：Chang-Kai Guo1 ; Yi Wang1 ; Tao Zhou1 ; Hong Yu ; Wen-Juan Zhang ; Wei-Jia Kong ; entwjkong@yahoo.com.cn
- 关键词：2 ; 5-dd-Ado ; 2 ; 5-dideoxyadenosine ; 4-DAMP ; 4-dipheylacetoxy-N-[2-chloroethyl]piperidine ; KCa ; Ca2+-dependent K+ channels ; APE ; arecaidine propargyl ester ; ACh ; acetylcholine ; AC ; adenyl cyclase ; BK ; big-conductance KCa channel ; CCh ; carbamyl-尾-methylcholi
- 刊名：Hearing Research
- 出版年：2012
- 期刊代码：111_03785955
- 类别：med
- 出版时间：March, 2012
- 卷：285
- 期：1-2
- 页码：13-19
- 文件大小：698 K
摘要
There are two types of hair cells in the sensory epithelium of vestibular end organ. Type II vestibular hair cell (VHC II) is innervated by the efferent nerve endings, which employ a cholinergic inhibition mediated by SK channels through the activation of 伪9-containing nAChR. Our previous studies demonstrated that a BK-type cholinergic inhibition was present in guinea pig VHCs II, which may be mediated by an unknown mAChR. In this study, BK channel activities triggered by ACh were studied to determine the mAChR subtype and function. We found the BK channel was insensitive to 伪9-containing nAChR antagonists and m1, m3, m4 muscarinic antagonists, but potently inhibited by the m2 muscarinic antagonist. Muscarinic agonists could mimic the effect of ACh and be blocked by m2 antagonist. cAMP analog activated the BK current and adenyl cyclase (AC) inhibitor inhibited the ACh response. Inhibitor of Gi伪 subunit failed to affect the BK current, but inhibitor of Gi伪 and Gi尾纬 subunits showed a potent inhibition to these currents. Our findings provide the physiological evidence that mAChRs may locate in guinea pig VHCs II, and m2 mAChRs may play a dominant role in BK-type cholinergic inhibition. The activation of m2 mAChRs may stimulate Gi尾纬-mediated excitation of AC/cAMP activities and lead to the phosphorylation of Ca2+ channels, resulting in the influx of Ca2+ and opening of the BK channel.