Photochemical regulation of calcium in cell physiology

细胞生理学中钙的光化学调节

• 批准号: 8134080
• 负责人: Graham Ellis-Davies
• 金额: $ 25.84万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-02-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8134080
• 关键词: 4-methoxy-7-nitroindolinyl-glutamate; Acinar Cell; Affinity; Agonist; Alzheimer' s Disease; Animals; Astrocytes; Biological; Biology; Biomedical Research; Brain; British Columbia; Caffeine; Calcium; Calcium Signaling; Calcium-Sensing Receptors; Cell membrane; Cell physiology; Cells; Cellular biology; Chemicals; Chemistry; Chloride Channels; Collaborations; Communities; Consultations; Cultured Cells; Dendritic Spines; Dependence; Development; Disease; Dyes; Egtazic Acid; Epilepsy; Esters; Event; Excitatory Postsynaptic Potentials; Exocytosis; Experimental Designs; Farming environment; Figs - dietary; Funding; Gene Expression Process; Generic Drugs; Germany; Glutamates; Goals; Grant; ITPR1 gene; Image; Imagery; In Situ; Individual; Kinetics; Laboratories; Lasers; Life; Light; Mammalian Cell; Maps; Mediating; Microscope; Modeling; Mus; Nature; Neurobiology; Nicotine; Nicotine Dependence; Nicotinic Receptors; Optics; Peptides; Pharmaceutical Preparations; Photons; Physiological; Physiology; Preparation; Process; Property; Regulation; Research; Research Personnel; Ryanodine Receptor Calcium Release Channel; Ryanodine Receptors; Scientist; Second Messenger Systems; Signal Transduction; Site; Slice; Source; Status Epilepticus; Structure; Synapses; Synaptic Potentials; Techniques; Technology; Testing; Time; Tissues; Tokyo; Ultraviolet Rays; Universities; Variant; Vertebral column; Viola; Wound Healing; absorption; addiction; analog; base; caged IP3; chemical synthesis; chromophore; design; experience; improved; in vivo; memory encoding; mouse model; new technology; photolysis; prevent; quantum; second messenger; success; two-photon

DESCRIPTION (provided by applicant): Calcium is the single most important messenger molecule in mammalian cells. Fluctuations in its concentration control a myriad of processes from gene expression to wound healing. The goal of this proposal is the chemical synthesis of photochemically based probes that will be used to control calcium concentration in living animals. New laser and microscope technologies now permit the imaging of structures as small single synapses in vivo. We wish to use this technology (the two-photon microscope) to be more than passive observers of cell function. We propose to make chemical probes that will allow us to actively intervene in the calcium dynamics of individual cells in vivo. To do this we will take advantage of a new chromophore we have recently made (called "NDBF"), that is uniquely sensitive to two-photon excitation. We will develop functionally inert (or "caged") derivatives of IPS or calcium receptor agonists that are photochemically liberated by two-photon photolysis. These new probes will be used in collaboration with other scientists to study how basic calcium-regulated processes encode memory at the level of single synapses. They will also be used, in concert with two-photon imaging of calcium, to probe the dynamics of calcium signaling in mouse models of disease states such epilepsy and Alzheimer's, as well as during nicotine addiction. Calcium signaling is significantly perturbed by these states. The photochemical probes we propose to develop will enable us to examine these changes in living animals for the first time.

描述（由申请人提供）：钙是哺乳动物细胞中最重要的信使分子。其浓度的波动控制着从基因表达到伤口愈合的无数过程。该提案的目标是基于光化学的探针的化学合成，该探针将用于控制活体动物中的钙浓度。新的激光和显微镜技术现在允许在体内将结构成像为小的单个突触。我们希望利用这项技术（双光子显微镜）不仅仅是被动观察细胞功能。我们建议制作化学探针，使我们能够积极干预体内单个细胞的钙动力学。为了做到这一点，我们将利用我们最近制造的一种新的发色团（称为“NDBF”），它对双光子激发非常敏感。我们将开发IPS或钙受体激动剂的功能惰性（或“笼”）衍生物，这些衍生物通过双光子光解光化学释放。这些新的探针将与其他科学家合作，研究基本的钙调节过程如何在单突触水平上编码记忆。它们还将与钙的双光子成像相结合，用于探测癫痫和阿尔茨海默氏症等疾病状态的小鼠模型以及尼古丁成瘾期间钙信号的动力学。钙信号被这些状态显著干扰。我们计划开发的光化学探针将使我们能够第一次在活体动物中检查这些变化。