CELLULAR CONTROL OF SALIVARY BUFFER CAPACITY

碳酸氢盐浓度（HCOminus）的主函数 唾液的作用是缓冲口腔pH值的变化。 HCOminus 由唾液腺的腺泡细胞分泌，通过 受环核苷酸控制的氯离子通道， 胞浆钙 因此，我得出结论，唾液缓冲能力是在 部分直接受第二信使浓度的调节， 腺泡细胞的细胞质。 在本申请中，我将表明， pHi和细胞质pH之间存在紧密的负相关关系， 钙 工作假设是细胞质氢离子（即， pHi）抑制活化期间的钙内流。 这一假设预测， 从腮腺细胞流出的HCO负离子是一种自限性的 现象（即，负反馈调节涉及2个胞质 离子-钙和氢）。 我的初步证据显示 细胞质钙受pHi的影响， 关系 也有证据表明，Na+/Ca++交换和 膜表面钙泵对pH敏感。 如果这 假设可以被证明，那么这将建立如何腺泡细胞 分泌HCOminus，而不损害他们自己的缓冲能力， 引起细胞活化的pHi降低。 此外，这项研究 会给我们提供线索，让我们了解 在活化过程中钙的内流，这是一个主要的争议点。 本申请中的实验将：1）建立关系 pHi和细胞质钙之间的精确定量关系，以及2） 表征钙离子的pH敏感性转运蛋白。 这 信息对于建立调查基础至关重要， 存在控制腺泡细胞的负反馈调节 physiology.

The principal function of the bicarbonate concentration (HCOminus) of saliva is to buffer changes in the pH of the oral cavity. HCOminus is secreted by the acinar cells of the salivary glands into the lumen through the chloride channel which is under the control of cyclic nucleotides and cytoplasmic calcium. Thus I conclude that salivary buffer capacity is in part directly regulated by the concentration of secondary messengers in the cytoplasm of acinar cells. In this application, I shall show that there is a tight, inverse relationship between pHi and cytoplasmic calcium. The working hypothesis is that cytoplasmic hydrogen ions (i.e., pHi) inhibit calcium influx during activation. This hypothesis predicts that the efflux HCOminus from the parotid cell is a self-limiting phenomenon (i.e., negative feedback regulation involving 2 cytoplasmic ions--calcium and hydrogen). My preliminary evidence shows that cytoplasmic calcium is influenced by pHi in a directly varying relationship. There is also evidence that the Na+/Ca++ exchange and calcium pump of the surface membrane is sensitive to pHi. If this hypothesis could be proven, then this would establish how acinar cells secreted HCOminus without jeopardizing their own capacity to buffer the decrease in pHi that occasions cellular activation. Also this research would give us clues s to the nature of the mechanism responsible for the influx of calcium during activation which is a point of major controversy. The experiments in this application will: 1) establish the relationship between pHi and cytoplasmic calcium in precise, quantitative terms and 2) characterize the pHi-sensitive transporters of calcium ions. This information is essential to establish a foundation for investigating the presence of negative-feedback regulation that controls acinar cell physiology.