Departments of Ophthalmology & Visual Sciences and Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48105, USA.
Int J Mol Sci. 2021 Jun 28;22(13):6935. doi: 10.3390/ijms22136935.
By providing ~70% of the eye's refractive power, the preocular tear film is essential for optimal vision. However, its integrity is often jeopardized by environmental and pathologic conditions that accelerate evaporation and cause sight-impairing dry eye. A key adaptive response to evaporation-induced tear film hyperosmolarity is the reflex-triggered release of tear-stabilizing mucin from conjunctival goblet cells. Here, we review progress in elucidating the roles of ion channels in mediating this important exocytotic response. Much is now known about the modulatory impact of ATP-sensitive potassium channels, nonspecific cation channels and voltage-gated calcium channels. Recently, we discovered that during unremitting extracellular hyperosmolarity, P2X receptor/channels also become activated and markedly impair goblet cell viability. However, our understanding of possible adaptive benefits of this P2X activation remains limited. In the present study, we utilized high-temporal resolution membrane capacitance measurements to monitor the exocytotic activity of single goblet cells located in freshly excised rat conjunctiva. We now report that activation of P2X purinoceptors boosts neural-evoked exocytosis and accelerates replenishment of mucin-filled granules after exocytotic depletion. Thus, P2X activation exerts a yin-yang effect on conjunctival goblet cells: the high-gain benefit of enhancing the supply of tear-stabilizing mucin is implemented at the high-risk of endangering goblet cell survival.
通过提供约 70%的眼睛折射力，预眼的泪膜对于最佳视力至关重要。然而，其完整性常常受到环境和病理条件的威胁，这些条件会加速蒸发并导致视力受损的干眼症。蒸发引起的泪膜高渗的一个关键适应反应是反射触发结膜杯状细胞释放稳定泪液的粘蛋白。在这里，我们回顾了阐明离子通道在介导这种重要的胞吐反应中的作用的进展。现在已经了解了 ATP 敏感性钾通道、非特异性阳离子通道和电压门控钙通道的调节作用。最近，我们发现，在持续的细胞外高渗环境下，P2X 受体/通道也被激活，并显著损害杯状细胞的活力。然而，我们对这种 P2X 激活可能带来的适应性益处的理解仍然有限。在本研究中，我们利用高时间分辨率的膜电容测量来监测位于新鲜分离的大鼠结膜中的单个杯状细胞的胞吐作用。我们现在报告，P2X 嘌呤能受体的激活增强了神经诱发的胞吐作用，并加速了胞吐作用耗尽后粘蛋白填充颗粒的补充。因此，P2X 的激活对结膜杯状细胞产生了一种阴阳效应：增强稳定泪液的粘蛋白供应的高增益益处是以危及杯状细胞生存为高风险实现的。
