Vision Research Center, University of Missouri-Kansas City, School of Medicine, Kansas City, Missouri 64108, USA.
Invest Ophthalmol Vis Sci. 2011 Jul 29;52(8):5605-11. doi: 10.1167/iovs.10-7114.
Lacrimal glands regulate the production and secretion of tear fluid. Dysfunction of lacrimal gland acinar cells can ultimately result in ocular surface disorders, such as dry eye disease. Ca(2+) homeostasis is tightly regulated in the cellular environment, and secretion from the acinar cells of the lacrimal gland is regulated by both cholinergic and adrenergic stimuli, which both result in changes in the cytosolic Ca(2+) concentration. We have previously described the detailed intracellular distribution of inositol-1,4,5-trisphosphate receptors (IP(3)Rs), and ryanodine receptors (RyRs) in lacrimal acinar cells, however, little is known regarding the expression and distribution of the third major class of intracellular Ca(2+) release channels, transient receptor potential polycystin family (TRPP) channels.
Studies were performed in adult lacrimal gland tissue of Swiss-Webster mice. Expression, localization, and intracellular distribution of TRPP Ca(2+) channels were investigated using immunocytochemistry, immunohistochemistry, and electron microscopy. The biophysical properties of single polycystin-2 channels were investigated using a planar lipid bilayer electrophysiology system.
All channel-forming isoforms of TRPP channels (polycystin-2, polycystin-L, and polycystin-2L2) were expressed in adult mouse lacrimal gland. Subcellular analysis of immunogold labeling revealed strongest polycystin-2 expression on the membranes of the endoplasmic reticulum, Golgi, and nucleus. Biophysical properties of lacrimal gland polycystin-2 channels were similar to those described for other tissues.
The expression of TRPP channels in lacrimal acinar cells suggests a functional role of the proteins in the regulation of lacrimal fluid secretion under physiological and disease conditions, and provides the basis for future studies focusing on physiology and pharmacology.
泪腺调节泪液的产生和分泌。泪腺腺泡细胞功能障碍最终可导致眼表面疾病,如干眼症。细胞环境中钙(Ca 2+)稳态受到严格调节,泪腺腺泡细胞的分泌受胆碱能和肾上腺素能刺激调节,这两种刺激均导致细胞浆 Ca 2+浓度的变化。我们之前描述了在泪腺腺泡细胞中肌醇 1,4,5-三磷酸受体(IP 3 Rs)和兰尼碱受体(RyRs)的详细细胞内分布,然而,关于第三大类细胞内 Ca 2+释放通道,瞬时受体电位多囊蛋白家族(TRPP)通道的表达和分布知之甚少。
在瑞士-韦伯斯特小鼠的成年泪腺组织中进行了研究。使用免疫细胞化学、免疫组织化学和电子显微镜研究了 TRPP Ca 2+通道的表达、定位和细胞内分布。使用平面脂质双层电生理学系统研究了单个多囊蛋白-2 通道的生物物理特性。
TRPP 通道的所有通道形成同工型(多囊蛋白-2、多囊蛋白-L 和多囊蛋白-2L2)均在成年小鼠泪腺中表达。免疫金标记的亚细胞分析显示,多囊蛋白-2 在内质网膜、高尔基复合体和核上的表达最强。泪腺多囊蛋白-2 通道的生物物理特性与其他组织中描述的相似。
TRPP 通道在泪腺腺泡细胞中的表达表明这些蛋白在调节生理和疾病条件下的泪液分泌中具有功能作用,并为未来专注于生理学和药理学的研究提供了基础。