Lewandowski Brian C, Sukumaran Sunil K, Margolskee Robert F, Bachmanov Alexander A
Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104
Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104.
J Neurosci. 2016 Feb 10;36(6):1942-53. doi: 10.1523/JNEUROSCI.2947-15.2016.
Responses in the amiloride-insensitive (AI) pathway, one of the two pathways mediating salty taste in mammals, are modulated by the size of the anion of a salt. This "anion effect" has been hypothesized to result from inhibitory transepithelial potentials (TPs) generated across the lingual epithelium as cations permeate through tight junctions and leave their larger and less permeable anions behind (Ye et al., 1991). We tested directly the necessity of TPs for the anion effect by measuring responses to NaCl and Na-gluconate (small and large anion sodium salts, respectively) in isolated taste cells from mouse circumvallate papillae. Using calcium imaging, we identified AI salt-responsive type III taste cells and demonstrated that they compose a subpopulation of acid-responsive taste cells. Even in the absence of TPs, many (66%) AI salt-responsive type III taste cells still exhibited the anion effect, demonstrating that some component of the transduction machinery for salty taste in type III cells is sensitive to anion size. We hypothesized that osmotic responses could explain why a minority of type III cells (34%) had AI salt responses but lacked anion sensitivity. All AI type III cells had osmotic responses to cellobiose, which were significantly modulated by extracellular sodium concentration, suggesting the presence of a sodium-conducting osmotically sensitive ion channel. However, these responses were significantly larger in AI type III cells that did not exhibit the anion effect. These findings indicate that multiple mechanisms could underlie AI salt responses in type III taste cells, one of which may contribute to the anion effect.
Understanding the mechanisms underlying salty taste will help inform strategies to combat the health problems associated with NaCl overconsumption by humans. Of the two pathways underlying salty taste in mammals, the amiloride-insensitive (AI) pathway is the least understood. Using calcium imaging of isolated mouse taste cells, we identify two separate populations of AI salt-responsive type III taste cells distinguished by their sensitivity to anion size and show that these cells compose subpopulations of acid-responsive taste cells. We also find evidence that a sodium-conducting osmotically sensitive mechanism contributes to salt responses in type III taste cells. Our data not only provide new insights into the transduction mechanisms of AI salt taste but also have important implications for general theories of taste encoding.
在介导哺乳动物咸味的两条途径之一的amiloride不敏感（AI）途径中，反应受到盐阴离子大小的调节。这种“阴离子效应”被假设是由于阳离子通过紧密连接渗透并留下其较大且渗透性较小的阴离子时，跨舌上皮产生的抑制性跨上皮电位（TPs）所致（Ye等人，1991年）。我们通过测量来自小鼠轮廓乳头的分离味觉细胞对NaCl和葡萄糖酸钠（分别为小阴离子和大阴离子钠盐）的反应，直接测试了TPs对阴离子效应的必要性。使用钙成像，我们鉴定了AI盐反应性III型味觉细胞，并证明它们构成酸反应性味觉细胞的一个亚群。即使在没有TPs的情况下，许多（66%）AI盐反应性III型味觉细胞仍然表现出阴离子效应，这表明III型细胞中咸味转导机制的某些成分对阴离子大小敏感。我们假设渗透反应可以解释为什么少数III型细胞（34%）具有AI盐反应但缺乏阴离子敏感性。所有AI III型细胞对纤维二糖都有渗透反应，并受到细胞外钠浓度的显著调节，表明存在一种钠传导的渗透敏感离子通道。然而，这些反应在未表现出阴离子效应的AI III型细胞中明显更大。这些发现表明，多种机制可能是III型味觉细胞中AI盐反应的基础，其中一种机制可能导致阴离子效应。
了解咸味的潜在机制将有助于为应对与人类过量摄入NaCl相关的健康问题提供策略。在哺乳动物咸味的两条途径中，amiloride不敏感（AI）途径是了解最少的。通过对分离的小鼠味觉细胞进行钙成像，我们鉴定了两个不同的AI盐反应性III型味觉细胞群体，它们通过对阴离子大小的敏感性来区分，并表明这些细胞构成酸反应性味觉细胞的亚群。我们还发现证据表明，一种钠传导的渗透敏感机制有助于III型味觉细胞中的盐反应。我们的数据不仅为AI盐味的转导机制提供了新的见解，也对味觉编码的一般理论具有重要意义。
