FUNCTION AND CHEMOMODULATION OF THE CUTANEOUS SA1 MECHANORECEPTOR COMPLEX

触摸式穹顶是一种低门槛机械传感结构，包括 专门的默克尔细胞的聚集和覆盖的一层 上皮性角质形成细胞。默克尔细胞，位于基底层 表皮，似乎是高度分化的上皮细胞， 是由大的有髓I型神经元支配的。类突触 连接与神经末梢最近的Merkel细胞质相连。 在触觉穹顶上方的上皮细胞中，特化现象明显。 因为与附近的上皮不同，它是强免疫阳性的 神经生长因子(NGF)。尽管默克尔的牢房位于理想的位置 作为主要的机械传感换能器，它们在 触摸式穹顶仍然存在争议。我们获得的初步证据 一种独特的体外皮肤神经制剂支持这一概念 神经递质5-羟色胺在默克尔细胞和 I型神经元首先被激活，然后产生模式 抑制I型传入反应。体外系统也将 被用来调查在 Merkel细胞/轴突复合体(三磷酸腺苷、甲硫氨酸脑啡肽和谷氨酸)。 互补免疫细胞化学研究将定位神经递质 触摸式穹顶上的接收器。致密岩心的仔细组织学计数 机械性压低触摸罩前后的水泡分布 也将进行分析小泡是否耗尽 伴随着现场的自然刺激。相似的体外生理学 形态技术将被应用于暴露的制剂 对阿尔法-乳杆菌毒素，一种会导致巨大水泡的蜘蛛毒液 从突触前终末释放。神经生长因子和神经生长因子的作用 位于Merkel细胞和I型传入神经元上的NGF受体将 通过评估脑内I型神经元的机械敏感性来研究 低亲和力或高亲和力NGF受体缺陷小鼠的活体实验 子类型。原位杂交实验将确定NGF是否 由触摸式穹顶角质形成细胞产生的隔离物。

Touch domes are low threshold mechanosensory structures consisting of aggrgates of specialized Merkel cells and an overlying layer of epithelial keratinocytes. Merkel cells, located in the basal layer of the epidermis, appear to be highly differentiated epithelial cells which are innervated by large myelinated type I neurons. Synapse-like junctions join Merkel cell cytoplasm nearest to the nerve ending. Specialization is evident in the epithelium overlying touch domes because unlike nearby epithelium, it is strongly immunopositive for nerve growth factor (NGF). Although Merkel cells are ideally situated to act as primary mechanosensory transducer, their functional role in touch domes remains controversial. Our preliminary evidence obtained from a unique iin vitro skin-nerve preparation supports the notion that the neurotransmitter serotonin found both in Merkel cells and type I neurons first activates, and subsequently produces modes inhibition of type I afferent responses. The in vitro system will also be utilized in investigate other transmitter substances found in the Merkel cell/neurite complex (ATP, met-enkephalin and glutamate). Complementar immunocytochemical studies will localize neurotransmitter receptorss in touch domes. Careful histological counts of dense-cored vesicle profiles before and after mechanical depression of touch domes will also be undertaken to analyze whethr vesicle depletion accompanies natural stimulation in situ. Similar in vitro physiological and morphological techniques will be applied to preparations exposed to alpha-Latrotoxin, a spider venom which causes massive vesicle release frompresynaptic terminals. The functional roleof NGF and NGF-receptors located on Merkel cells and type I afferent neurons will be investigated by assessing mechanosensitivity of type I neurons in vivo in mice deficient in either the low- or high-affinity NGF receptor subtype. In situ hybridazation experiments will determine if NGF is sequesteredor produced by touch dome keratinocytes.