唾液腺是非常重要的外分泌腺。在唾液腺分泌轴，腺泡和闰管细胞分泌初始唾液，颗粒导管和纹管对原始唾液中成份进行修饰，形成低渗透压，低[Na+]、[Cl-]，高[K+]、[HCO3-]的终极唾液。本文研究高钾和低渗对颌下腺纹管细胞[Ca2+]c信号的调控。研究发现在颌下腺纹管细胞，胞外高K+ (30, 50 mM)导致细胞膨胀，和细胞膜的去极化，但是对胞浆Ca2+没有影响。胞外高K+浓度(30, 50 mM)使ACh 或NE引发的Ca2+高台发生可逆性塌陷。NCX特异性拮抗剂KB-R7943 完全阻断高钾30 mM对ACh与NE 钙高台的塌陷作用，但对高钾50 mM的塌陷抑制不明显。KB-R7943的抑制作用取决于钙塌陷是否已经发生。 RT-PCR和细胞免疫化学试验证明颌下腺纹管细胞膜表达NCX1和NCX2，且NCX1主要存在于纹管细胞的管道侧质膜。揭示高钾在颌下腺纹管细胞通过细胞膜去极化，激活NCX的正向运转，刺激Ca2+外排，导致ACh和NE钙高台的塌陷。胞外低渗对颌下腺纹管细胞基础钙离子浓度在多数细胞影响。但胞外低渗导致ACh 或NE高台上的钙过射。胞外低渗的这种高台钙过射不被IP3R拮抗剂咖啡因或对机械牵张敏感的离子通道阻断剂GdCl3所抑制，但是可被TRPV抑制剂RR显著抑制。ACh高台上的胞外低渗钙过射可被TRPV2抑制剂SK&F96365所阻断，但是不阻断NE钙高台上的胞外低渗钙过射。NE钙高台上的钙过射可被CYP抑制剂miconazole所阻断。研究还发现，TRPV1拮抗剂capsazepine阻断胞外低渗的钙过射作用。RT-PCR和细胞免疫化学试验证明颌下腺纹管细胞表达TRPV1-4和TRPV6，其中TRPV1、2、4、6主要表达在纹管细胞质膜，而TRPV3主要分布在纹管细胞核。因而在颌下腺纹管细胞，胞外低渗透压导致ACh和NE钙高台上的钙过射信号；ACh钙高台上的钙过射信号是TRPV1、TRPV2所介导；而NE钙高台上的钙过射信号是TRPV1、TRPV4所介导的。

Salivary glands are important exocrine glands, where isotonic primary saliva is secreted by acinar cells and intercalated ducts, which subsequently is modified by granular tubules and striated ducts, with the final saliva being hypotonic, rich in K+. But a physiological role for such high potassium bathing acinar and ductal cells has never been fully elucidated. In the present work high potassium modulation of agonist-induced calcium increase was examined in isolated rat submandibular striated ducts. It was found that both NE and ACh induced dose-dependent plateau increases in cytosolic calcium concentration in rat submandibular striated ductal cells. A calcium plateau was well-maintained by NE (2 M) or ACh (5 M). High potassium (30 mM or 50 mM), although had no effect on basal calcium, readily induced a sustained depression of the elevated calcium plateau. Equal molar NMDG had no effect, although choline also induced a depression of the plateau. Striated ductal cell was depolarized in high potassium (30 mM or 50 mM) in the presence or absence of NE or ACh, but NMDG or choline did not. High potassium (30 mM) depression of the calcium plateau was completely blocked by the sodium/calcium exchanger (NCX) inhibitor KB-R7943 (5 M), use-dependently. A role for NCX was confirmed by mRNA expression and immunocytochemical localization of NCX1 to the luminal side of submandibular striated ductal cells. Although striated ductal cell became swollen in high potassium, this volume expansion contributed minimally towards the high potassium depression. This work therefore for the first time revealed that a physiological role for elevated extracellular potassium maybe to limit agonist-induced sustained calcium increase, by activating the sodium/calcium exchange mechanism which exists in the striated ductal cell. Hypotonicity was found to induce a robust calcium overshoot on the ACh or NE-maintained calcium plateau in freshly isolated rat submandibular striated ducts. The calcium overshoot was not affected by IP3R blocker caffeine or stretch-activated channel inhibitor GdCl3, but inhibited by ruthenium red, a blocker of both TRPV and RyR. The calcium overshoot on ACh calcium plateau was inhibited by SK&F96365, a TRPV2 inhibitor. The calcium overshoot on NE calcium plateau was blocked by the TRPV4 blocker miconazole. The calcium overshoot over both ACh and NE calcium plateay was blocked by TRPV1 antagonist capsazepine. RT-PCR and immunocytochemistry confirmed the expression of TRPV1-4 and TRPV6 in striated ductal cells. Together these data demonstrate involvement of TRPV1 and TRPV2 in calcium overshoot on the ACh calcium plateau, and involvement of TRPV1 and TRPV4 in calcium overshoot on NE calcium plateau.