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: 2856628
• 负责人: Katherine Janet Rennie
• 金额: $ 10.04万
• 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/2856628
• 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，并且这种调制的来源之一是通过发射机 从支配类型的萼末端的顶端区域释放 我细胞。 I 型毛细胞仅存在于羊膜动物中，是唯一的毛细胞 '受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端之间的突触传递 据信是化学介导的。 I型头发的去极化 假设细胞通过发束的偏转来增加 一种未知的神经递质的量，很可能是谷氨酸或 GABA， 从毛细胞中释放出来。 尽管已知花萼纤维可以编码 来自 I 型毛细胞的传入信息，形态学证据 表明花萼的上部区域可能释放神经活性物质 物质附着在毛细胞上。 此外，前庭传出纤维使 突触与肾盏膜外表面的接触。 因此 I 型毛细胞被认为是局部刺激下的突触前感觉细胞。 来自花萼的控制，也可能通过以下作用受到中央控制 花萼上的传出管。 单独 I 型细胞的记录表明 全细胞离子电流很大且大小可变。 它 假设这些电流可能受到生理调节， 明显的调制源是通过发射机释放 花萼。 I 型毛细胞电导的调节会改变头发 细胞对传感器电流的响应可以赋予相当大的 I 型机电信号处理的灵活性 毛细胞。 为了检验 I 型电流可以被调制的假设， 实验将在分离的沙鼠 I 型细胞上进行。 这 肾盏膜上受体的身份将通过以下方式确定 假定的传入和传出发射器（及其 拮抗剂和激动剂）到全细胞膜片钳中分离的肾盏或 到外面的补丁。 I 型细胞的原位记录将建立 肾盏接触的 I 型细胞中的离子电流是否与 分离细胞中的那些以及神经模拟对 I 型细胞的影响 将评估反应，以验证 I 型细胞电导是否符合 在反馈控制下。 这些实验的结果将提供 有关哺乳动物 I 型毛细胞突触生理学的信息以及 他们的花萼。