title: OSU-03012, a novel celecoxib derivative, induces cell swelling and shortens action potential duration in mouse ventricular cells.
abstract: OSU03012, a novel celecoxib derivative, has been shown to inhibit proliferation and induce apoptosis in numerous cancer cell lines. However, not much is known about its influence on cell volume regulation and cardiac function in the mammalian heart. We examined the effects of OSU-03012 on cell volume and action potentials in mouse ventricular cells. Video image analysis showed that cell volume increased on application of OSU-03012 in a dose-dependent manner. The action potential duration (APD) at 50% and 90% repolarization (APD(50) and APD(90) respectively) as well as the resting membrane potential (RMP) were measured in current-clamp experiments. OSU-03012 had little effect on APD(50) and RMP but induced approximately 30% shortening of APD(90). These results for cell volume and AP are similar to those in cells under ischaemia/hypoxia, and we confirmed that the shortening of APD(90) was almost completely recovered by glibenclamide, a potent inhibitor of ATP-sensitive potassium channels.We concluded that OSU-03012 may lead to cell swelling and shortening of AP via reduced ATP production in mouse ventricular cells.
authors.affiliation: Department of Pharmacology, School of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jyonan-ku, Fukuoka, Japan. yamamotos@fukuoka-u.ac.jp
authors.forename: Shintaro
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Iyoda
authors.forename: Satomi
authors.initials: S
authors.lastname: Kita
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yamada
authors.forename: Takahiro
authors.initials: T
authors.lastname: Iwamoto
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D000068579:Celecoxib; D048429:Cell Size; D005905:Glyburide / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology* / Q000187:drug effects; D054086:KATP Channels / Q000037:antagonists & inhibitors; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D054086:KATP Channels; C500894:OSU 03012; D011720:Pyrazoles; D013449:Sulfonamides; D000255:Adenosine Triphosphate; D000068579:Celecoxib; D005905:Glyburide