Modulation of Peripheral Gustatory Neurons by Organic Salts and Organic Acids

描述（由申请人提供）：味觉是一种关键的感觉系统，它作为一种工具，用于检测、识别和最终摄入钠（Na+），钠是生命不可或缺的必要营养素。NaCl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，并且从有记录的历史开始就一直如此。然而，今天，许多防腐剂的形式，有机钠+盐，大阴离子和有机酸被用于加工食品，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在整体感知咸度下降。因此，为了达到相同的咸味，加工食品中添加了更多的Na+，这导致Na+的过度消费，可能导致高血压的发展，这是美国的一种流行病。来自电生理学鼓索神经记录的支持证据已经表明，具有大阴离子的有机Na+盐以及酸性钠盐溶液降低鼓索神经反应。然而，令人惊讶的是，这些实验没有在单个神经元水平上进行检查，使得Na+味道的编码机制在很大程度上未知。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，而味觉场缺乏这种刺激分辨率，从而留下独特的放电模式，如刺激诱发的抑制，开-关，侧抑制等未知。因此，（在同事的帮助下）开发了EGG（Electrogustogram），以研究刺激应用的精确时刻，同时记录大鼠膝状体神经节中的单个神经元数小时，从而提供神经元反应曲线的详细分析。本实验旨在通过大鼠膝状体神经节的单单位神经生理学研究阴离子大小和酸度对Na+味觉的影响。将分别使用苯扎明和SB 366791（特异性ENaC和TRPV 1拮抗剂）确定上皮钠通道（ENaC）和瞬时受体电位香草酸受体1（TRPV 1）在Na+反应中的作用。具体目标1将表征来自阴离子大小不同的3种盐的盐响应曲线，以及对KCl的盐响应曲线，每种盐在4种浓度下，以及酸度对这些盐响应的影响。酸性食物被认为通过细胞内酸化降低Na+通过ENaC的电导率来降低食物的总体咸味。因此，具体目标2将评价在酸性和中性pH下存在有机酸的情况下味觉神经元类型的Na+响应。 公共卫生相关性：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。

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.