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: 6342336
• 负责人: Katherine Janet Rennie
• 金额: $ 10.08万
• 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/6342336
• 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，该调制的一个来源是通过发射机 从Calyx端子的顶端区域释放，该端子的支柱类型 I细胞。 I型毛细胞仅在羊膜中发现，是唯一的毛细胞 '由包围细胞基极的传入花萼支配。 I型细胞及其相关的花萼结束之间的突触传播 被认为是化学介导的。 I型头发的去极化 通过假定发束的挠度，细胞被认为会增加 数量不明的神经递质（最有可能是谷氨酸或GABA）的数量， 从毛细胞中释放。 尽管已知花萼纤维编码 来自I型毛细胞的传入信息，形态证据 表明花萼的上部区域可能会释放神经活性 物质上的毛细胞。 此外，前庭传出纤维使 与成钙膜外表面的突触接触。 因此 I型毛细胞被假定为局部的突触前感觉细胞 从花萼控制，也可能通过中心控制 花萼上的传出。 I型I型单元的录音表明 整个细胞离子电流较大且大小变化。 它 假设这些电流可能是生理调制的， 显而易见的调制源将是通过从发射机释放 花萼。 I型染发电池的调节会改变头发 电池对传感器电流的反应，该电流可能赋予大量 通过I型处理机械电信号的灵活性 毛细胞。 为了测试可以调制I型电流的假设， 实验将在离解的Gerbil I型细胞上进行。 这 在成绩原年膜上的受体身份将由 采用推定的传入和传染性发射机（及其 拮抗剂和激动剂）在全细胞贴剂钳或 到外面的补丁。 I型单元原位的录音将建立 通过钙接触的I型电池中的离子电流是否类似于 那些在孤立的细胞中以及神经模拟对I型细胞的影响 将评估响应，以验证I型细胞电导是否为 在反馈控制下。 这些实验的结果将提供 有关哺乳动物I型毛细胞和 他们的钙。