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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)
Publication Information
Molecules and Cells / v.22, no.1, 2006 , pp. 51-57 More about this Journal
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
Calcium; Haloperidol; Hippocampus; L-Type Calcium Channel; Oxidative Stress; Verapamil;
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1 Choi, D. W. (1988) Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage. Trends Neurosci. 11, 465−469   DOI   ScienceOn
2 Gil-ad, I., Shtaif, B., Shiloh, R., and Weizman, A. (2001) Evaluation of the neurotoxic activity of typical and atypical neuroleptics: relevance to iatrogenic extrapyramidal symptoms. Cell. Mol. Neurobiol. 21, 705−716   DOI   ScienceOn
3 Gomora, J. C., Daud, A. N., Weiergraber, M., and Perez-Reyes, E. (2001) Block of cloned human T-type calcium channels by succinimide antiepileptic drugs. Mol. Pharmacol. 60, 1121−1132
4 Roy, M. and Sapolsky, R. M. (2003) The exacerbation of hippocampal excitotoxicity by glucocorticoids is not mediated by apoptosis. Neuroendocrinology 77, 24−31   DOI   ScienceOn
5 Torreano, P. J. and Cohan, C. S. (2003) Calcium and voltage dependent inactivation of sodium calcium currents limits calcium influx in helisoma neuron. J. Neurobiol. 54, 439−456   DOI   ScienceOn
6 Rathi, S. S., Saini, H. K., Xu, Y. J., and Dhalla, N. S. (2004) Mechanisms of low Na+-induced increase in intracellular calcium in KCl-depolarized rat cardiomyocytes. Mol. Cell. Biochem. 263, 151−162   DOI
7 Siesjo, B. K., Bengtsson, F., Grampp, W., and Theander, S. (1989) Calcium, excitotoxins, and neuronal death in the brain. Ann. N. Y. Acad. Sci. 568, 234−251
8 Tsien, R. W., Lipscombe, D., Madison, D. V., Bley, K. R., and Fox, A. P. (1988) Multiple types of neuronal calcium channels and their selective modulation. Trends Neurosci. 11, 431−438   DOI   ScienceOn
9 Tseng, W. P. and Lin-Shiau, S. Y. (2003) Neuronal death signaling by beta-bungarotoxin through activation of the N-methyl- D-aspartate (NMDA) receptor L-type calcium channel. Biochem. Pharmacol. 65, 131−142   DOI   ScienceOn
10 Sattler, R. and Tymianski, M. (2001) Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death. Mol. Neurobiol. 24, 107−129   DOI   ScienceOn
11 Post, A., Holsboer, F., and Behl, C. (1998) Induction of NFkappaB activity during haloperidol-induced oxidative toxicity in clonal hippocampal cells: suppression of NF-kappaB and neuroprotection by antioxidants. J. Neurosci. 18, 8236−8246
12 Naidu, P. S. and Kulkarni, S. K. (2001) Excitatory mechanisms in neuroleptic-induced vacuous chewing movements (VCMs): possible involvement of calcium and nitric oxide. Behav. Pharmacol. 12, 209−216   DOI   ScienceOn
13 Takahashi, T., Kimoto, T., Tanabe, N., Hattori, T. A., Yasumatsu, N., et al. (2002) Corticosterone acutely prolonged NMDA receptor- mediated calcium elevation in cultured rat hippocampal neurons. J. Neurochem. 83, 1441−1451
14 Thayer, S. A., Usachev, Y. M., and Pottorf, W. J. (2002) Modulating $Ca^{2+}$ clearance from neurons. Front. Biosci. 7, d1255− 1279   DOI
15 Fern, R. (1988) Intracellular calcium and cell death during ischemia in neonatal rat white matter astrocytes in situ. J. Neurosci. 18, 7232−7243
16 Meredith, G. E., Switzer, R. C. 3rd., and Napier, T. C. (2004) Short-term D2 receptor blockade induces synaptic degeneration, reduces levels of tyrosine hydroxylase and brainderived neurotrophic factor, and enhances D2-mediated firing in the ventral pallidum. Brain Res. 995, 14−22   DOI   ScienceOn
17 Siesjo, B. K. (1989) Calcium and cell death. Magnesium 8, 223−237
18 Santi, C. M., Cayabyab, F. S., Sutton, K. G., McRory, J. E., Mezeyova, J., et al. (2002) Differential inhibition of T-type calcium channels by neuroleptics. J. Neurosci. 22, 396−403
19 Turrone, P., Remington, G., and Nobrega, J. N. (2002) The vacuous chewing movement (VCM) model of tardive dyskinesia revisited: is there a relationship to dopamine D (2) receptor occupancy- Neurosci. Biobehav. Rev. 26, 361−380   DOI   ScienceOn
20 Anderson, J. E., Wible, C. G., McCarley, R. W., Jakab, M., Kasai, K., et al. (2002) An MRI study of temporal lobe abnormalities and negative symptoms in chronic schizophrenia. Schizophr. Res. 58, 123−134
21 Cullen, P. J. and Lockyer, P. J. (2002) Integration of calcium and ras signaling. Nat. Rev. Mol. Cell. Biol. 3, 339−348
22 Bean, B. P. (1988) Classes of calcium channels in vertebrate cells. Annu. Rev. Physiol. 51, 367−384   DOI   ScienceOn