Modulation of Peripheral Gustatory Neurons by Organic Salts and Organic Acids

有机盐和有机酸对周围味觉神经元的调节

• 批准号: 7809341
• 负责人: Joseph Michael Breza
• 金额: $ 3.27万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7809341
• 关键词: Accounting; Acidity; Acids; Affect; American; Anions; Anterior; Apical; Cations; Cell membrane; Cells; Characteristics; Chemical Stimulation; Citric Acid; Code; Color; Consumption; Detection; Developed Countries; Development; Diffusion; Electrolytes; Epidemic; Epithelial; Facial nerve structure; Food; Food Preservatives; Food Processing; Frequencies; General Practitioners; Hour; Human; Hypertension; Individual; Ingestion; Lateral; Left; Life; Mediating; Membrane; Nerve; Neurons; Nutrient; Pattern; Peripheral; Probability; Rattus; Recording of previous events; Relative (related person); Resolution; Risk; Role; Salts; Shunt Device; Sodium; Sodium Channel; Sodium Chloride; Solutions; Specialist; Stimulus; Structure of geniculate ganglion; Synapses; System; Taste Perception; Testing; Time; Tongue; Variant; benzamil; chorda tympani; design; epithelial Na+ channel; food flavor; insight; instrument; neurophysiology; organic acid; prevent; public health relevance; receptor; relating to nervous system; research study; response; sensory system; vanilloid receptor subtype 1

DESCRIPTION (provided by applicant): Taste is a critical sensory system which acts as an instrument, in the detection, recognition, and ultimately ingestion of sodium (Na+), a necessary nutrient indispensable to life. NaCI, the prototypical salt stimulus, is used as a food preservative and additive to increase the flavor of foods and has been so since the beginning of recorded history. Today however, many preservatives in the form of organic Na+ salts, with large anions and organic acids are used in processed foods to increase shelf life, maintain color, and prevent caking, etc. The effect of these additives is generally a decrease in the overall perceived saltiness. Hence, more Na+ is added to processed foods in order to achieve the same saltiness, which results in over consumption of Na+, possibly leading to development of hypertension, an American epidemic. Supporting evidence from electrophysiological chorda tympani nerve recordings have shown that organic Na+ salts with large anions as well as acidic sodium salt solutions, reduce the chorda tympani nerve response. Surprisingly however, these experiments have not been examined on a single neuron level, leaving coding mechanisms of Na+ taste largely unknown. Moreover, a critical variable in cracking neural codes for any sensory system is knowing when the stimulus reaches the receptors and the taste field lacks this stimulus resolution leaving unique firing patterns such as stimulus-evoked inhibition, on-off, lateral-inhibition, etc unknown. Accordingly, (with the help of a colleague) developed the Electrogustogram (EGG) in order to investigate the precise moment of stimulus application while simultaneously recording from single neurons in the rat geniculate ganglion for several hours, thereby providing detailed analyses of neuron response profiles. The following experiments are designed to examine the effects of anion size and acidity on Na+ taste by single unit neurophysiology in the rat geniculate ganglion. The role of the epithelial sodium channel (ENaC) and the transient receptor potential vanilloid receptor 1 (TRPV1) in Na+ responses will be determined using benzamil and SB366791, specific ENaC and TRPV1 antagonists, respectively. Specific aim 1 will characterize the salt response profiles from 3 monosodium salts that vary in anion size, and to KCI, each at 4 concentrations, and the effect of acidity on these salt responses. Acidic foods are thought to decrease the overall saltiness of food, by decreasing the conductance of Na+ though ENaC via intracellular acidification. Thus, Specific aim 2 will evaluate Na+ responses from gustatory neuron types in the presence of organic acids at acidic and at a neutral pH. PUBLIC HEALTH RELEVANCE: Understanding the peripheral gustatory coding mechanisms of Na+ can provide insight into the over-consumption of Na+ via processed foods.

描述（由申请人提供）：味觉是一个关键的感觉系统，在检测、识别和最终摄入钠（Na+）（生命不可缺少的必需营养素）方面充当仪器。氯化钠是典型的盐刺激物，被用作食品防腐剂和添加剂以增加食品的风味，自有记录以来一直如此。然而，如今，许多以有机Na+盐、大量阴离子和有机酸形式存在的防腐剂被用于加工食品中，以延长保质期、保持颜色、防止结块等。这些添加剂的效果通常是降低整体的防腐剂含量。感知到的咸味。因此，为了达到同样的咸味，加工食品中添加了更多的Na+，导致Na+摄入过多，可能导致美国流行的高血压病的发生。电生理学鼓索神经记录的支持证据表明，含有大量阴离子的有机 Na+ 盐以及酸性钠盐溶液可降低鼓索神经反应。然而令人惊讶的是，这些实验尚未在单个神经元水平上进行检查，因此 Na+ 味觉的编码机制在很大程度上是未知的。此外，破解任何感觉系统的神经密码的一个关键变量是知道刺激何时到达受体，而味场缺乏这种刺激分辨率，从而导致独特的放电模式，如刺激诱发的抑制、开关、横向抑制等未知。因此，（在同事的帮助下）开发了味电图（EGG），以便研究施加刺激的精确时刻，同时记录大鼠膝状神经节中单个神经元的数小时，从而提供神经元反应概况的详细分析。以下实验旨在通过大鼠膝状神经节的单个单元神经生理学检查阴离子大小和酸度对 Na+ 味觉的影响。上皮钠通道 (ENaC) 和瞬时受体电位香草酸受体 1 (TRPV1) 在 Na+ 反应中的作用将分别使用特定 ENaC 和 TRPV1 拮抗剂 benzamil 和 SB366791 来确定。具体目标 1 将表征 3 种阴离子大小不同的单钠盐和 KCI（每种在 4 个浓度下）的盐响应曲线，以及酸度对这些盐响应的影响。酸性食物被认为可以通过细胞内酸化降低 Na+ 通过 ENaC 的电导，从而降低食物的整体咸味。因此，特定目标 2 将评估在酸性和中性 pH 下存在有机酸的情况下味觉神经元类型的 Na+ 反应。 公共健康相关性：了解 Na+ 的外周味觉编码机制可以深入了解加工食品中 Na+ 的过度消耗。