Modulation of Peripheral Gustatory Neurons by Organic Salts and Organic Acids

描述(申请人提供)：味觉是一个关键的感官系统，在检测、识别和最终摄取钠(Na+)的过程中起着仪器的作用，钠是生命不可或缺的必要营养。NaCI是典型的食盐刺激剂，被用作食物防腐剂和添加剂，以增加食物的味道，从有记录的历史开始就是这样。然而，今天，许多以有机钠盐、大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、保持颜色和防止结块等。这些添加剂的效果通常是降低总体感觉的咸味。因此，为了达到同样的咸度，加工食品中添加了更多的Na+，这导致了Na+的过度消耗，可能会导致高血压的发展，这是美国的一种流行病。来自电生理鼓索神经记录的证据表明，含有大阴离子的有机钠盐以及酸性钠盐溶液，降低了鼓索神经的反应。然而，令人惊讶的是，这些实验并没有在单个神经元水平上进行检查，这使得Na+味道的编码机制基本上是未知的。此外，在破解任何感觉系统的神经密码时，一个关键变量是知道刺激何时到达感受器，而味觉区域缺乏这种刺激分辨率，使得独特的放电模式，如刺激诱发的抑制、开关、侧向抑制等未知。因此，(在一位同事的帮助下)开发了胃电图仪(EGG)，以研究施加刺激的准确时刻，同时记录大鼠膝状神经节中的单个神经元数小时，从而提供神经元反应谱的详细分析。用单单位神经生理学方法研究阴离子大小和酸度对大鼠膝状神经节Na+味觉的影响。上皮性钠通道(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用苯扎米和SB366791这两种特异性ENaC和TRPV1拮抗剂来确定。具体目标1将描述阴离子大小不同的3种单钠盐对KCI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盐度。因此，特定的目标2将评估在酸性和中性pH存在的有机酸存在下味觉神经元类型的Na+反应。 公共卫生相关性：了解Na+的外周味觉编码机制可以为通过加工食品过度摄入Na+提供洞察。

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.