OSU-03012, a novel celecoxib derivative, induces cell swelling and shortens action potential duration in mouse ventricular cells

  • Yamamoto Shintaro
    Department of Pharmacology, School of Medicine, Fukuoka University, Fukuoka, Japan
  • Iyoda Takuya
    Department of Pharmacology, School of Medicine, Fukuoka University, Fukuoka, Japan
  • Kita Satomi
    Department of Pharmacology, School of Medicine, Fukuoka University, Fukuoka, Japan
  • Yamada Toshiki
    Department of Pharmacology, School of Medicine, Fukuoka University, Fukuoka, Japan
  • Iwamoto Takahiro
    Department of Pharmacology, School of Medicine, Fukuoka University, Fukuoka, Japan

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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 (APD50 and APD90 respectively) as well as the resting membrane potential (RMP) were measured in current-clamp experiments. OSU-03012 had little effect on APD50 and RMP but induced approximately 30% shortening of APD90. These results for cell volume and AP are similar to those in cells under ischaemia/hypoxia, and we confirmed that the shortening of APD90 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.

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