title: L-carnitine reduces in human conjunctival epithelial cells hypertonic-induced shrinkage through interacting with TRPV1 channels.
abstract: OBJECTIVE
  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, Ca(2+) 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 ≈ 450 mOsM both induced increases in Ca(2+) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Charité - Universitätsmedizin Berlin, Campus Virchow-Clinic, Department of Ophthalmology, Berlin, Germany.
authors.forename: Noushafarin
authors.initials: N
authors.lastname: Khajavi
authors.forename: Peter S
authors.initials: PS
authors.lastname: Reinach
authors.forename: Marek
authors.initials: M
authors.lastname: Skrzypski
authors.forename: Anja
authors.initials: A
authors.lastname: Lude
authors.forename: Stefan
authors.initials: S
authors.lastname: Mergler
mesh_terms: D002331:Carnitine / Q000494:pharmacology*; D003228:Conjunctiva / Q000166:cytology / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D018408:Patch-Clamp Techniques; D034741:RNA, Small Interfering / Q000235:genetics; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D002331:Carnitine