Haloperidol Induces Calcium Ion Influx Via L-Type Calcium Channels in Hippocampal HN33 Cells and Renders the Neurons More Susceptible to Oxidative Stress

  • Kim, Hyeon Soo (Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology) ;
  • Yumkham, Sanatombi (Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology) ;
  • Choi, Jang Hyun (Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology) ;
  • Kim, Eung-Kyun (Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology) ;
  • Kim, Yong Sik (Department of Psychiatry and Behavioral Sciences and Institute of Human Behavioral Medicine, Seoul National University Hospital) ;
  • Ryu, Sung Ho (Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology) ;
  • Suh, Pann-Ghill (Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology)
  • Received : 2006.03.09
  • Accepted : 2006.06.14
  • Published : 2006.08.31

Abstract

Haloperidol is a classical neuroleptic drug that is still in clinical use and can lead to abnormal motor activity following repeated administration. However, there is little knowledge of how it triggers neuronal impairment. In this study, we report that it induced calcium ion influx via L-type calcium channels and that the elevation of calcium ions induced by haloperidol appeared to render hippocampal cells more susceptible to oxidative stress. Indeed, the level of cytotoxic reactive oxygen species (ROS) and the expression of pro-apoptotic Bax increased in response to oxidative stress in haloperidol-treated cells, and these effects were inhibited by verapamil, a specific L-type calcium channel blocker, but not by the T-type calcium channel blocker, mibefradil. These findings indicate that haloperidol induces calcium ion influx via L-type calcium channels and that this calcium influx influences neuronal fate.

Keywords

Acknowledgement

Supported by : Ministry of Commerce, Industry and Energy (MOCIE)

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