Zhu Yun, Kong Wei-Jia, Xia Jiao, Zhang Yu, Cheng Hua-Mao, Guo Chang-Kai
Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Sheng Li Xue Bao. 2008 Jun 25;60(3):375-81.
To confirm the existence of cholinergic receptors on type I vestibular hair cells (VHCs I) of guinea pigs and to study the properties of the cholinergic receptor-mediated ion channels on VHCs I, electrophysiological responses of isolated VHCs I to external ACh were examined by means of whole-cell patch-clamp recordings. The results showed that 7.5% (21/279) VHCs I were found to be sensitive to ACh (10-1000 μmol/L). ACh generated an outward current in a steady, slow, dose-dependent [EC(50) was (63.78±2.31) μmol/L] and voltage-independent manner. In standard extracellular solution, ACh at the concentration of 100 μmol/L triggered a calcium-dependent current of (170±15) pA at holding potential of -50 mV, and the current amplitude could be depressed by extracellularly added calcium-dependent potassium channel antagonist TEA. The time interval for the next complete activation of ACh-sensitive current was no less than 1 min. The ion channels did not shut off even when they were exposed to ACh for an extended period of time (8 min). The results suggest that dose-dependent, calcium-dependent and voltage-independent cholinergic receptors were located on a few of the VHCs I investibular epithelium of guinea pigs. The cholinergic receptors did not show desensitization to ACh. This work reveals the existence of efferent neurotransmitter receptors on VHCs I and helps in understanding the function of vestibular efferent nervous system, and may provide some useful information on guiding the clinical rehabilitative treatment of vertigo.
为证实豚鼠I型前庭毛细胞（VHCs I）上胆碱能受体的存在，并研究VHCs I上胆碱能受体介导的离子通道特性，采用全细胞膜片钳记录技术检测了分离的VHCs I对外源性乙酰胆碱（ACh）的电生理反应。结果显示，发现7.5%（21/279）的VHCs I对ACh（10 - 1000 μmol/L）敏感。ACh以稳定、缓慢、剂量依赖性[半数有效浓度（EC50）为（63.78±2.31）μmol/L]且电压非依赖性方式产生外向电流。在标准细胞外溶液中，100 μmol/L的ACh在 - 50 mV的钳制电位下引发了（170±15）pA的钙依赖性电流，且该电流幅度可被细胞外添加的钙依赖性钾通道拮抗剂四乙铵（TEA）抑制。ACh敏感电流下一次完全激活的时间间隔不少于1分钟。即使长时间（8分钟）暴露于ACh，离子通道也不会关闭。结果表明，剂量依赖性、钙依赖性和电压非依赖性胆碱能受体存在于豚鼠前庭上皮的少数VHCs I上。胆碱能受体对ACh不表现出脱敏现象。这项工作揭示了VHCs I上存在传出神经递质受体，有助于理解前庭传出神经系统的功能，并可能为指导眩晕的临床康复治疗提供一些有用信息。
