FUNCTION AND CHEMOMODULATION OF THE CUTANEOUS SA1 MECHANORECEPTOR COMPLEX

触摸圆顶是低阈值机械感觉结构， 由特化的默克尔细胞的聚集体和覆盖在其上的 上皮角质形成细胞 默克尔细胞，位于基底层， 表皮似乎是高度分化上皮细胞， 由大型有髓I型神经元支配。类突触 连接最靠近神经末梢的默克尔细胞质。 在覆盖触球的上皮细胞中有明显的特化 因为与附近的上皮不同，它对以下免疫反应呈强阳性： 神经生长因子（NGF）。 虽然默克尔牢房的位置很理想 作为主要的机械感觉换能器，它们在 触摸圆顶仍然存在争议。 我们的初步证据显示 从一个独特的体外皮肤神经准备支持的概念， 在默克尔细胞中发现的神经递质血清素， I型神经元首先激活，随后产生模式 抑制I型传入反应。 体外系统还将 用于研究在 默克尔细胞/神经突复合物（ATP、甲硫氨酸脑啡肽和谷氨酸）。 补充免疫细胞化学研究将定位神经递质 在触摸圆顶的接收器。 仔细的组织学计数 触觉圆顶机械按压前后的囊泡轮廓 也将进行分析， 伴随着原地的自然刺激。 相似的体外生理 形态学技术将应用于 一种蜘蛛毒液，会导致巨大的水泡 从突触前末梢释放。 神经生长因子的功能作用， 位于默克尔细胞和I型传入神经元上的NGF受体将 通过评估I型神经元的机械敏感性来研究， 在低或高亲和力NGF受体缺陷的小鼠体内 亚型 原位杂交实验将确定NGF是否 由接触圆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.