期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 34, 期 3, 页码 790-803出版社
KARGER
DOI: 10.1159/000363043
关键词
Human conjunctival epithelium; L-carnitine; Transient receptor potential channels; Calcium; Osmoprotectants; Cell volume; Planar patch clamp technique; Capsaicin receptor
资金
- DFG [Me 1706/13-1, Me 1706/14-1]
- Berliner Sonnenfeld-Stiftung [89745052]
Background/Aims: Ocular surface health depends on conjunctival epithelial (HCjE) layer integrity since it protects against pathogenic infiltration and contributes to tissue hydration maintenance. As the same increases in tear film hyperosmolarity described in dry eye disease can increase corneal epithelial transient receptor potential vanilloid type -1 (TRPV1) channel activity, we evaluated its involvement in mediating an osmoprotective effect by L-carnitine against such stress. Methods: Using siRNA gene silencing, Ca2+ imaging, planar patch clamping and relative cell volume measurements, we determined if the protective effects of this osmolyte stem from its interaction with TRPV1. Results: TRPV1 activation by capsaicin (CAP) and an increase in osmolarity to approximate to 450 mOsM both induced increases in Ca2+ levels. In contrast, blocking TRPV1 activation with capsazepine (CPZ) fully reversed this response. Similarly, L-carnitine (1 mM) also reduced underlying whole-cell currents. In calcein-AM loaded cells, hypertonic-induced relative cell volume shrinkage was fully blocked during exposure to L-carnitine. On the other hand, in TRPV1 gene silenced cells, this protective effect by L-carnitine was obviated. Conclusion: The described L-carnitine osmoprotective effect is elicited through suppression of hypertonic-induced TRPV1 activation leading to increases in L-carnitine uptake through a described Na+-dependent L-carnitine transporter Copyright (C) 2014 S Karger AG, Basel
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