VOLTAGE-DEPENDENT ION CHANNELS IN GUSTATION

味觉中电压相关的离子通道

• 批准号: 7849533
• 负责人: LIQUAN HUANG
• 金额: $ 31.72万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-14 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7849533
• 关键词: Afferent Neurons; Ageusia; Animals; Behavioral; Behavioral tic; Biochemical; Biochemistry; Bioinformatics; Biological Assay; Brain; Calcium; Calcium Channel; Cell membrane; Cells; Code; Coupled; Cranial Nerves; Development; Dominant-Negative Mutation; Dyes; Dysgeusia; Electrical Synapse; Electrophysiology (science); Esthesia; Event; Functional Magnetic Resonance Imaging; GTP-Binding Proteins; Genes; Genetic; Human; Hypogeusia; Ion Channel; KCNQ1 protein; Knock-out; Knockout Mice; Knowledge; Label; Lead; Length; Literature; Mediating; Membrane; Membrane Potentials; Methods; Modality; Molecular; Molecular Biology; Molecular Cloning; Molecular and Cellular Biology; Monitor; Monovalent Cations; Nerve; Nerve Fibers; Neuraxis; Neurons; Organ; PHluorin; Pathway interactions; Perception; Peripheral; Physiological; Process; Property; Protein Isoforms; Protein Subunits; Proteins; RNA Interference; RNA Splicing; Receptor Cell; Receptor Signaling; Research; Research Personnel; Role; Signal Transduction; Signal Transduction Pathway; Signaling Molecule; Site; Small Interfering RNA; Stimulus; Surface; Synapses; Synaptic Transmission; Synaptic Vesicles; TRPM5 gene; Taste Bud Cell; Taste Buds; Taste Disorders; Taste Perception; Techniques; Testing; Variant; Wild Type Mouse; afferent nerve; base; behavior test; cell type; channel blockers; effective therapy; insight; loss of function; mouse genome; mutant; novel; overexpression; paracrine; programs; receptor; relating to nervous system; response; tongue papilla; transmission process; voltage

DESCRIPTION (provided by applicant): Taste perception is initiated by the interaction of sapid molecules with proteins on the surface of taste bud cells. These gustatory signals are subsequently transduced, processed in taste buds, coded and transmitted by cranial nerves to the brain. The long-term objective of our research program is to molecularly identify and functionally characterize key proteins that are involved in taste signal transduction and coding in taste buds, and decoding in the central nervous system, and eventually to reconstruct the molecular events of taste sensation and perception. We have used molecular cloning and functional analyses to identify and characterize a number of taste transduction components, including a G-protein coupled taste receptor T1R3, G protein subunits and a transient receptor potential ion channel TRPM5. In order to understand the molecular events downstream of TRPM5 and to reveal ion channels that are responsible for sour and salty tastes, we have determined the expression of six voltage-dependent calcium channels in taste bud cells. The specific aims of this proposal are: 1) to identify and colocalize voltage-dependent calcium channel subunits with known taste signaling molecules in taste bud cells; 2) to heterologously express and functionally characterize novel isoforms of these voltage-dependent calcium channels isolated from taste buds; 3) to determine possible roles of these voltage-dependent calcium channels in taste bud synaptic transmission by monitoring the effect of pharmacological and genetic perturbation of these channels on the elevation of intracellular calcium concentrations and synaptic activity in taste bud cells in response to taste stimuli; 4) finally, to determine possible roles of these voltage-dependent calcium channels in taste sensation by gustatory nerve recording and animal behavioral tests with mutant animals. The results of these studies will yield new insights into the molecular mechanisms underling sour, salt, bitter, sweet and umami taste transduction, synaptic transmission and peripheral coding in the end organs of taste. The knowledge gained from this endeavor will further our understanding of the molecular bases of taste disorders such as malgeusia, dysgeusia, hypogeusia and ageusia and may lead to effective treatment.

描述(申请人提供)：味觉是由味蕾细胞表面的皂基分子与蛋白质相互作用而产生的。这些味觉信号随后被传导，在味蕾中处理，由脑神经编码并传输到大脑。我们研究计划的长期目标是从分子上鉴定和鉴定在味蕾中参与味觉信号转导和编码的关键蛋白，以及在中枢神经系统中参与解码的关键蛋白，最终重建味觉和知觉的分子事件。我们利用分子克隆和功能分析鉴定和鉴定了一些味觉转导成分，包括G蛋白偶联的味觉受体T1R3、G蛋白亚基和瞬时受体电位离子通道Trpm5。为了了解Trpm5下游的分子事件，并揭示导致酸味和咸味的离子通道，我们测定了味蕾细胞中六种电压依赖性钙通道的表达。该建议的具体目的是：1)鉴定并定位味蕾细胞中已知的味觉信号分子的电压依赖性钙通道亚单位；2)异源表达这些从味蕾中分离的电压依赖性钙通道的新亚型，并对其功能进行表征；3)通过监测这些通道的药理和遗传扰动对味蕾细胞内钙浓度的升高和突触活性的影响，确定这些电压依赖性钙通道在味蕾突触传递中的可能作用；4)最后，通过味觉神经记录和突变动物的动物行为测试，确定这些电压依赖性钙通道在味觉感觉中的可能作用。这些研究结果将对酸、盐、苦、甜和鲜味转导、突触传递和味觉末端器官外周编码的分子机制产生新的见解。从这一努力中获得的知识将进一步加深我们对味觉障碍如味觉障碍、味觉障碍、味觉减退和失语的分子基础的理解，并可能导致有效的治疗。