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

描述(申请人提供)：哺乳动物的体感系统可以检测到各种各样的机械刺激，如质地、形状、振动或压力。这种不同的刺激与不同的机械敏感体感神经元阵列相匹配。皮肤中的非神经细胞，如角质形成细胞，也可能与感觉神经元协调传递力。这项提议的目的是确定躯体感觉机械转导的分子和细胞机制。我们假设初级传入躯体感觉神经元和角质形成细胞都在皮肤中介导机械敏感反应。我们将使用包括活细胞钙成像、电生理学和药理学在内的各种技术来表征感觉神经元和角质形成细胞中的转导通道。然后我们将探索候选通道在体内的作用。这些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转导触摸的离子通道的分子特性是什么？2)角质形成细胞中的触摸诱发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?