PHARMACOLOGY OF THE TYPE I HAIR CELL/CALYX SYNAPSE

I 型毛细胞/花萼突触的药理学

• 批准号: 2471004
• 负责人: Katherine Janet Rennie
• 金额: $ 9.13万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2471004
• 关键词: ear hair cell; gamma aminobutyrate; gerbil /jird; glutamates; neuropharmacology; neurotransmitter antagonist; organ culture; potassium channel; potassium ion; synapses; voltage /patch clamp

DESCRIPTION: Experiments described in this proposal will address the hypothesis that the membrane properties of type I Vestibular hair cells can be modulated and that one source of this modulation is through transmitter release from the apical regions of the calyx terminals which innervate type I cells. Type I hair cells, found only in amniotes, are the only hair cells 'innervated by an afferent calyx that encases the basal pole of the cell. Synaptic transmission between type I cell and its associated calyceal ending is believed to be chemically mediated. Depolarization of the type I hair cell, through deflection of the hair bundle, is assumed to increase the amount of an unidentified neurotransmitter, most likely glutamate or GABA, released from the hair cell. Although the calyx fiber is known to encode afferent information from the type I hair cell, morphological evidence suggests that the upper regions of the calyx may release neuroactive substances onto the hair cell. In addition, Vestibular efferent fibers make synaptic contact with the outer face of the calyceal membrane. Thus the type I hair cell is postulated to be a presynaptic sensory cell under local control from the calyx and also possibly under central control via action of the efferents on the calyx. Recordings from solitary type I cells indicate that the whole cell ionic currents are large and variable in magnitude. It is hypothesized that these currents may be physiologically modulated, an obvious source of modulation would be through transmitter release from the calyx. Modulation of type I hair cell conductances would alter the hair cell's response to transducer current which could confer considerable flexibility on the processing of mechanoelectrical signals by the type I hair cell. To test the hypothesis that type I currents can be modulated, experiments will be carried out on dissociated gerbil type I cells. The identity of receptors on the calyceal membrane will be established by application of putative afferent and efferent transmitters (and their antagonists and agonists) to isolated calyces in whole cell patch-clamp or to outside out patches. Recordings from type I cells in situ will establish whether ionic currents in type I cells contacted by calyces are similar to those in isolated cells and the effects of nerve simulation on type I cell responses will be assessed, to verify whether type I cell conductances are under feedback control. Results from these experiments will provide information on the synaptic physiology of mammalian type I hair cells and their calyces.

描述：本提案中描述的实验将解决 假设I型前庭毛细胞的膜特性可以 被调制，并且该调制的一个源是通过发射机 从支配类型的花萼末端的顶端区域释放 I细胞。I型毛细胞是唯一的毛细胞，只存在于羊膜细胞中。 ‘由包围细胞基极的传入花萼支配。 I型细胞与其相关的肾盏末梢之间的突触传递 被认为是由化学物质介导的。I型毛发的去极化 细胞，通过发束的偏转，被认为增加了 不明神经递质的数量，很可能是谷氨酸或GABA， 从毛细胞中释放出来。尽管已知的花萼纤维编码 来自I型毛细胞的传入信息，形态证据 提示花萼的上部区域可能释放神经活性 物质进入毛细胞。此外，前庭传出纤维使 突触与肾盏膜的外表面接触。因此， I型毛细胞可能是局灶性突触前感觉细胞 从花萼控制，也可能在中央控制下，通过 花萼上的传出纤维。孤立的I型细胞的记录表明 整个细胞的离子电流都很大，而且大小可变。它 假设这些电流可能是生理上调制的， 调制的明显来源将是通过发射机从 卡利克斯。I型毛细胞电导的调节会改变头发 电池对传感器电流的响应，这可能会带来相当大的影响 第一类机电信号处理的灵活性 毛细胞。为了测试I类电流可以被调制的假设， 实验将在分离的沙土鼠I型细胞上进行。这个 肾盏膜上受体的特性将通过以下方式确定 假定传入和传出传送器的应用(及其 拮抗剂和激动剂)对全细胞膜片钳或 到外面的补丁。来自原位I型细胞的记录将证实 与花萼接触的I型细胞中的离子电流是否类似于 神经刺激对I型细胞的影响 将对响应进行评估，以验证I型电池电导是否 在反馈控制下。这些实验的结果将提供 哺乳动物I型毛细胞的突触生理学信息和 他们的花冠。