A human TREK-1/HEK cell line: a highly efficient screening tool for drug development in neurological diseases.
TREK-1 potassium channels are involved in a number of physiopathological processes such as neuroprotection, pain and depression. Molecules able to open or to block these channels can be clinically important. Having a cell model for screening such molecules is of particular interest. Here, we describe the development of the first available cell line that constituvely expresses the TREK-1 channel. The TREK-1 channel expressed by the h-TREK-1/HEK cell line has conserved all its modulation properties. It is opened by stretch, pH, polyunsaturated fatty acids and by the neuroprotective molecule, riluzole and it is blocked by spadin or fluoxetine. We also demonstrate that the h-TREK-1/HEK cell line is protected against ischemia by using the oxygen-glucose deprivation model.
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique (UMR6097), Université de Nice Sophia Antipolis, Valbonne, France.
Hamid
H
Moha ou Maati
Rémi
R
Peyronnet
Christelle
C
Devader
Julie
J
Veyssiere
Fabien
F
Labbal
Carine
C
Gandin
Jean
J
Mazella
Catherine
C
Heurteaux
Marc
M
Borsotto
D015687:Cell Hypoxia / Q000187:drug effects; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells / Q000166:cytology*; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects; D009422:Nervous System Diseases / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D024683:Potassium Channels, Tandem Pore Domain / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000378:metabolism; D019782:Riluzole / Q000494:pharmacology; D013314:Stress, Mechanical
D005231:Fatty Acids, Unsaturated; D018696:Neuroprotective Agents; D010455:Peptides; D024683:Potassium Channels, Tandem Pore Domain; D011956:Receptors, Cell Surface; C103742:potassium channel protein TREK-1; C551795:spadin peptide; D005473:Fluoxetine; D049452:Green Fluorescent Proteins; D019782:Riluzole