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

描述（由申请人提供）：哺乳动物体感系统检测各种机械刺激，如纹理，形状，振动或压力。这种不同的刺激与不同的机械敏感体感觉神经元相匹配。皮肤中的非神经元细胞，如角质形成细胞，也可能与感觉神经元协调传导力。本研究的目的是确定躯体感觉机械传导的分子和细胞机制。我们假设初级传入体感觉神经元和角化细胞都介导皮肤的机械敏感反应。我们将使用各种技术，包括活细胞Ca2+成像，电生理学和药理学来表征感觉神经元和角化细胞的转导通道。然后，我们将探讨候选通道在体内的作用。提出的实验将回答关于体感觉机械转导的基本问题，包括：1)在感觉神经元和角化细胞中转导触觉的离子通道的分子特性是什么？2)角化细胞中触摸诱发的信号如何改变初级传入神经元的功能？

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?