Wikström M A, Lawoko G, Heilbronn E
Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska institutet, Stockholm, Sweden.
J Physiol Paris. 1998 Oct-Dec;92(5-6):345-9. doi: 10.1016/S0928-4257(99)80003-5.
Outer hair cells (OHC) of the mammalian cochlea modulate the inner hair cell (IHC) mechanoelectrical transduction of sound. They are contacted by synapsing efferent neurons from the CNS, their main efferent neurotransmitter being acetylcholine (ACh). OHC function and in particular their control of [Ca2+]i is highly important and is modulated by ACh and also by other substances including extracellular (EC) ATP. OHC carry at their efferent synapse a not yet completely identified neuronal type of ionotropic ACh receptor (AChR), with an unusual pharmacology, which is, in vivo and in vitro, reversibly blocked by alpha-bungarotoxin (alpha-bgtx). The AChR mediates a fast influx of Ca2+ into OHC which, in turn, activates a closeby located outwardly-directed Ca(2+)-dependent K(+)-channel, thus shortly hyperpolarizing the cell. A cloned homomeric alpha 9 nAChR mimicks the function and pharmacology of this receptor. We here report results from a study designed to observe only slower effects triggered by EC ATP and the ACh-AChR system. EC presence of ATP at OHC increases [Ca2+]i by activating both P2x and P2y purinoceptors and also by indirect activation of OHC L-type Ca(2+)-channels. The L-type channel activation is responsible for a large part of the [Ca2+]i increase. Simultaneous EC presence of ACh and ATP at OHC was found to depress ATP-induced effects on OHC [Ca2+]i, an effect that is completely blocked in the presence of alpha-bgtx. Our observations suggest that the ACh-AChR system is involved in the modulation of the observed EC ATP-triggered events; possibly the OHC AChR is able to act both in its well known rapid ionotropic way, but also, perhaps after modification in a slower, metabotropic way interfering with the EC ATP-induced [Ca2+]i increase.
哺乳动物耳蜗的外毛细胞（OHC）可调节内毛细胞（IHC）的声音机械电转导。中枢神经系统的传出神经元通过突触与它们接触，其主要传出神经递质是乙酰胆碱（ACh）。OHC的功能，尤其是它们对细胞内钙离子浓度（[Ca2+]i）的控制非常重要，且受到ACh以及包括细胞外（EC）ATP在内的其他物质的调节。OHC在其传出突触处携带一种尚未完全确定的神经元型离子型ACh受体（AChR），其药理学特性不同寻常，在体内和体外均可被α-银环蛇毒素（α-bgtx）可逆性阻断。该AChR介导Ca2+快速流入OHC，进而激活附近的外向型Ca(2+)-依赖性K(+)通道，从而使细胞短暂超极化。一种克隆的同聚体α9烟碱型AChR模拟了该受体的功能和药理学特性。我们在此报告一项研究的结果，该研究旨在观察仅由EC ATP和ACh-AChR系统触发的较慢效应。OHC处EC存在ATP可通过激活P2x和P2y嘌呤受体以及间接激活OHC的L型Ca(2+)通道来增加[Ca2+]i。L型通道的激活是[Ca2+]i增加的主要原因。发现在OHC处同时存在ACh和ATP可抑制ATP对OHC [Ca2+]i的诱导作用，在存在α-bgtx的情况下该效应完全被阻断。我们的观察结果表明，ACh-AChR系统参与了对观察到的EC ATP触发事件的调节；可能OHC的AChR既能以其众所周知的快速离子型方式起作用，也可能在经过修饰后以较慢的代谢型方式起作用，从而干扰EC ATP诱导的[Ca2+]i增加。
