Roles and functions of ion channels that mediate mammalian touch transduction.

描述（由申请人提供）：哺乳动物的体感系统检测各种各样的机械刺激，如纹理、形状、振动或压力。这种刺激的多样性是匹配的机械敏感的躯体感觉神经元的多样性阵列。皮肤中的非神经元细胞，如角质形成细胞，也可以与感觉神经元协调以抵抗力。这个建议的目标是确定分子和细胞机制的体感机械转导。我们推测，初级传入体感神经元和角质形成细胞介导的皮肤机械敏感反应。我们将使用各种技术，包括活细胞钙离子成像，电生理学和药理学的特点转导通道的感觉神经元和角质形成细胞。然后，我们将探讨候选通道在体内的作用。所提出的实验将回答有关体感机械转导的基本问题，包括：1）感觉神经元和角质形成细胞中接触的离子通道的分子身份是什么？以及2）角质形成细胞中的触摸诱发的信号传导如何改变初级传入神经元功能？

DESCRIPTION (provided by applicant): The mammalian somatosensory system detects a wide variety of mechanical stimuli, such as texture, shape, vibration or pressure. This variety of stimuli is matched by a diverse array of mechanosensitive somatosensory neurons. Non-neuronal cells in the skin, such as keratinocytes, may also coordinate with sensory neurons to transduce force. The goal of this proposal is to identify molecular and cellular mechanisms underlying somatosensory mechanotransduction. We hypothesize that both primary afferent somatosensory neurons and keratinocytes mediate mechanosensitive responses in the skin. We will use a variety of techniques including live-cell Ca2+ imaging, electrophysiology and pharmacology to characterize transduction channels in sensory neurons and keratinocytes. We will then probe the role of candidate channels in vivo. The proposed experiments will answer fundamental questions about somatosensory mechanotransduction, including: 1) What are the molecular identities of the ion channels that transduce touch in sensory neurons and keratinocytes? and 2) How does touch-evoked signaling in keratinocytes alter primary afferent neuron function?