外毛细胞上胆碱能受体的体外药理学特性研究

In vitro pharmacologic characterization of a cholinergic receptor on outer hair cells.

作者信息

Erostegui C, Norris C H, Bobbin R P

机构信息

Department of Otolaryngology, Tulane University School of Medicine, New Orleans LA.

出版信息

Hear Res. 1994 Apr;74(1-2):135-47. doi: 10.1016/0378-5955(94)90182-1.

DOI:10.1016/0378-5955(94)90182-1

PMID:8040084

Abstract

Acetylcholine (ACh) is the major neurotransmitter released from the efferent fibers in the cochlea onto the outer hair cells (OHCs). The type of ACh receptor on OHCs and the events subsequent to receptor activation are unclear. Therefore we studied the effect of agonists and antagonists of the ACh receptor on isolated OHCs from the guinea pig. OHCs were recorded from in whole cell voltage and current clamp configuration. ACh induced an increase in outward K+ current (IACh) which hyperpolarized the OHCs. No desensitization to ACh application was observed. Cs+ replaced K+ in carrying the IACh. The IACh is Ca(2+)-dependent, time and voltage sensitive, and different from the IKCa induced by depolarization of the membrane potential. When tested at 100 microM, several agonists also induced outward current responses (acetylcholine > suberyldicholine > or = carbachol > DMPP) whereas nicotine, cytisine and muscarine did not. The IACh response to 10 microM ACh was blocked by low concentrations of traditional and non-traditional-nicotinic antagonists (strychnine > curare > bicuculline > alpha-bungarotoxin > thimethaphan) and by higher concentrations of muscarinic antagonists (atropine > 4-DAMP > AF-DX 116 > pirenzepine). Pharmacologically, the ACh receptor on OHCs is nicotinic.

摘要

乙酰胆碱（ACh）是从耳蜗传出纤维释放到外毛细胞（OHC）上的主要神经递质。OHC 上 ACh 受体的类型以及受体激活后的事件尚不清楚。因此，我们研究了 ACh 受体激动剂和拮抗剂对豚鼠分离的 OHC 的影响。在全细胞电压和电流钳模式下记录 OHC。ACh 诱导外向 K⁺电流（IACh）增加，使 OHC 超极化。未观察到对 ACh 应用的脱敏现象。Cs⁺在携带 IACh 时替代了 K⁺。IACh 是 Ca²⁺依赖性的，对时间和电压敏感，且不同于由膜电位去极化诱导的 IKCa。当在 100 μM 下测试时，几种激动剂也诱导外向电流反应（乙酰胆碱＞辛二酰胆碱＞或 = 卡巴胆碱＞二甲基苯基哌嗪），而尼古丁、金雀花碱和毒蕈碱则没有。对 10 μM ACh 的 IACh 反应被低浓度的传统和非传统烟碱拮抗剂（士的宁＞箭毒＞荷包牡丹碱＞α-银环蛇毒素＞三甲硫吩）以及高浓度的毒蕈碱拮抗剂（阿托品＞4-二甲基氨基吡啶＞AF-DX 116＞哌仑西平）阻断。从药理学角度来看，OHC 上的 ACh 受体是烟碱型的。