Voltage-Gated Calcium Channels in Nociceptors and Mechanoreceptors

伤害感受器和机械感受器中的电压门控钙通道

基本信息

  • 批准号:
    10656868
  • 负责人:
  • 金额:
    $ 8.33万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-08-01 至 2026-07-31
  • 项目状态:
    未结题

项目摘要

Voltage-gated calcium ion channels are critically important proteins that regulate release of glutamate and substance P from nociceptors in the superficial dorsal horn of the spinal cord. As such, they serve as the gatekeepers, at the junction of the periphery and central nervous system, conveying information about touch, heat, mechanical stimulation and more to the brain. High heat or strong mechanical stimuli are noxious and perceived in the brain as painful. Neurons that detect potentially harmful signals, such as high heat, are essential for protecting the body against damage. In response to continued stimulation, such as occurs in tissue injury, these neurons can sensitize as part of a protective response, but their sensitivity usually returns to normal after healing. In certain chronic pain conditions, such as after peripheral nerve injury, the sensitivity of nociceptors fails to return to pre injury levels and normal heat and touch continue to be perceived as painful. This persistence of sensitization combined with ongoing spontaneous activity of pain circuits can result in unrelenting, chronic pain. Understanding the molecular and cellular changes that occur during the transition from normal to chronic pain states are the key to improving current – inadequate – therapies. This proposal builds on our recent discoveries and our unique expertise to determine the role of voltage-gated calcium ion channels in sensory neurons that contribute to chronic pain. We study Cacna1a and Cacna1b genes that encode the core subunits of two calcium ion channels, CaV2.1 and CaV2.2, that control transmitter release at the majority of synapses in the mammalian nervous system. We tackle two critically important questions in our overall objective to elucidate the molecular mechanisms that orchestrate Cacna1a and Cacna1b processing and their actions in different subtypes of sensory neurons that transmit information about thermal and mechanical stimuli: Aim 1. What cellular factors control the expression of the major forms of CaV2 channels in thermal and mechanical signaling? What molecular changes disrupt the normal pattern of expression of these calcium ion channels in chronic pain? Aim 2. How do different calcium ion channels function in thermal and mechanical signaling at peripheral nerve endings in skin? And do the abnormal expression patterns of different forms of ion channels contribute to the induction and maintenance of abnormal signaling? Our research addresses major gaps in our understanding, and the results will contribute to new strategies and reveal new targets for pharmacological or genetic approaches, to mitigate certain forms of chronic pain experienced by millions of people in the United States.
电压门控钙离子通道是调节谷氨酸和谷氨酸释放的重要蛋白

项目成果

期刊论文数量(0)
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会议论文数量(0)
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Diane Lipscombe其他文献

Diane Lipscombe的其他文献

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{{ truncateString('Diane Lipscombe', 18)}}的其他基金

Single nucleotide polymorphisms of neuronal CACNA1C L-type calcium channels assoc
神经元CACNA1C L型钙通道关联的单核苷酸多态性
  • 批准号:
    7995239
  • 财政年份:
    2009
  • 资助金额:
    $ 8.33万
  • 项目类别:
Single nucleotide polymorphisms of neuronal CACNA1C L-type calcium channels assoc
神经元CACNA1C L型钙通道关联的单核苷酸多态性
  • 批准号:
    7785050
  • 财政年份:
    2009
  • 资助金额:
    $ 8.33万
  • 项目类别:
Neuroscience Advanced Predoctoral institutional Training Grant
神经科学高级博士前机构培训补助金
  • 批准号:
    8666954
  • 财政年份:
    2008
  • 资助金额:
    $ 8.33万
  • 项目类别:
Neuroscience Advanced Predoctoral institutional Training Grant
神经科学高级博士前机构培训补助金
  • 批准号:
    9519050
  • 财政年份:
    2008
  • 资助金额:
    $ 8.33万
  • 项目类别:
Neuroscience Advanced Predoctoral institutional Training Grant
神经科学高级博士前机构培训补助金
  • 批准号:
    9309079
  • 财政年份:
    2008
  • 资助金额:
    $ 8.33万
  • 项目类别:
Neuroscience Advanced Predoctoral institutional Training Grant
神经科学高级博士前机构培训补助金
  • 批准号:
    8875783
  • 财政年份:
    2008
  • 资助金额:
    $ 8.33万
  • 项目类别:
Neuroscience Advanced Predoctoral institutional Training Grant
神经科学高级博士前机构培训补助金
  • 批准号:
    9102284
  • 财政年份:
    2008
  • 资助金额:
    $ 8.33万
  • 项目类别:
N-type Calcium Channels in Nociceptive Neurons
伤害感受神经元中的 N 型钙通道
  • 批准号:
    7424984
  • 财政年份:
    2006
  • 资助金额:
    $ 8.33万
  • 项目类别:
N-type Calcium Channels in Nociceptive Neurons
伤害感受神经元中的 N 型钙通道
  • 批准号:
    7271103
  • 财政年份:
    2006
  • 资助金额:
    $ 8.33万
  • 项目类别:
N-type Calcium Channels in Nociceptive Neurons
伤害感受神经元中的 N 型钙通道
  • 批准号:
    7088279
  • 财政年份:
    2006
  • 资助金额:
    $ 8.33万
  • 项目类别:

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脊髓传入神经元如何控制食欲和口渴
  • 批准号:
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  • 批准号:
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  • 财政年份:
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Neurobiology of Intrinsic Primary Afferent Neurons
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  • 财政年份:
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Neurobiology of Intrinsic Primary Afferent Neurons
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  • 批准号:
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  • 财政年份:
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Neurobiology of Intrinsic Primary Afferent Neurons
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  • 财政年份:
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GPR35 on Vagal Afferent Neurons as a Peripheral Drug Target for Treating Diet-Induced Obesity
迷走神经传入神经元上的 GPR35 作为治疗饮食引起的肥胖的外周药物靶点
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  • 批准号:
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  • 财政年份:
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机械感觉离子通道在肌间固有初级传入神经元中的作用
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