CFTR-regulated chloride transport at the ocular surface in living mice measured by potential differences
CFTR-regulated chloride transport at the ocular surface in living mice measured by potential differences
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DOI：
10.1167/iovs.04-1314
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发表时间：
2005-04-01
影响因子：
4.4
通讯作者：
Verkman, AS
中科院分区：
文献类型：
--
作者：
Levin, MH;Verkman, AS
目的.目的探讨囊性纤维化跨膜传导调节因子（CFTR）在小鼠眼表Cl-分泌中的作用。在麻醉的野生型和囊性纤维化（CF）小鼠中，测量了对Cl-离子替代和转运激动剂和转运体的反应，即跨越液体浴眼表面的开路电位差（PD）。基础眼表PD为-23 +/- 1 mV（SE; 20只野生型小鼠），阿米洛利后去极化至-16 +/- 2 mV，低Cl-后超极化至-34 +/- 3 mV。通过毛喉素或选择性激活剂激活CFTR引起进一步持续的超极化至-50至+/- 60 mV。UTP产生了一个可比的，但短暂的超极化。CFTR抑制剂CFTRinh-172和GlyH-101在很大程度上逆转了激动剂-但不是低Cl-诱导的超极化。CF小鼠的PD在低Cl-后超极化2.1 mV，并且对CFTR激活剂或转运体不敏感。CFTR提供了小鼠眼表Cl-分泌的主要途径，表明CFTR激活剂作为干眼治疗的应用。阿米洛利敏感性Na+转运蛋白促进Na+吸收。PD测量提供了一种评估眼表面离子转运机制的可靠且可重复的方法。
PURPOSE. To define the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in Cl- secretion at the mouse ocular surface in vivo.METHODS. Open-circuit potential differences (PDs) across the fluid-bathed ocular surface were measured in anesthetized wild-type and cystic fibrosis (CF) mice in response to Cl- ion substitution and transport agonists and inhibitors.RESULTS. Basal ocular surface PD was -23 +/- 1 mV (SE; 20 wild-type mice), depolarizing to -16 +/- 2 mV after amiloride, then hyperpolarizing to -34 +/- 3 mV after low Cl-. CFTR activation by forskolin or a selective activator caused further sustained hyperpolarization to -50 to +/- 60 mV. UTP produced a comparable but transient hyperpolarization. The CFTR inhibitors CFTRinh-172 and GlyH-101 largely reversed agonist- but not low Cl--induced hyperpolarizations. PD in CF mice hyperpolarized by 2.1 mV after low Cl- and was insensitive to CFTR activators or inhibitors.CONCLUSIONS. CFTR provides a major pathway for mouse ocular surface Cl- secretion, suggesting the application of CFTR activators as therapy for dry eye. Amiloride-sensitive Na+ transporters facilitate Na+ absorption. PD measurements provide a robust and reproducible means of assessing ocular surface ion transporting mechanisms.