QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 5, 2003, 23(31):10093-10099

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (43) Citing Articles via Google Scholar Google Scholar Articles by Stevens, T. R. Articles by Picciotto, M. R. Search for Related Content PubMed PubMed Citation Articles by Stevens, T. R. Articles by Picciotto, M. R.

 Previous Article  |  Next Article 

Cellular/Molecular
Neuroprotection by Nicotine in Mouse Primary Cortical Cultures Involves Activation of Calcineurin and L-Type Calcium Channel Inactivation

Tanya R. Stevens,¹ Stefan R. Krueger,² Reiko M. Fitzsimonds,² and Marina R. Picciotto¹

Departments of ¹Psychiatry and ²Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06508

Regulation of intracellular calcium influences neuronal excitability, synaptic plasticity, gene expression, and neurotoxicity. In this study, we investigated the role of calcium in mechanisms underlying nicotine-mediated neuroprotection from glutamate excitotoxicity. Neuroprotection by nicotine in primary cortical cultures was not seen in knock-out mice lacking the 2 subunit of the nicotinic acetylcholine receptor (nAChR). Neuroprotection was partially blocked in wild-type cultures by -bungarotoxin, an antagonist of the 7 nAChR subtype, suggesting a potential cooperative role for these subtypes. Pretreatment with nicotine decreased glutamate-mediated calcium influx in primary cortical cultures by 41%, an effect that was absent in cultures from knock-out mice lacking the 2 subunit of the nAChR. This effect was dependent on calcium entry through L-type channels during nicotine pretreatment in wild-type cultures. The ability of nicotine to decrease glutamate-mediated calcium influx was occluded by cotreatment with nifedipine during glutamate application, suggesting that nicotine pretreatment decreased subsequent activity of L-type calcium channels. Treatment with the calcineurin antagonists FK506 and cyclosporine during pretreatment eliminated both nicotine-mediated neuroprotection and the effects of nicotine on L-type channels. We conclude that neuroprotective effects of nicotine in cortical neurons involve both 2- and 7-containing nAChRs, activation of calcineurin, and decreased intracellular calcium via L-type channels.

Key words: calcium imaging; cell death; glutamate; FK506; nifedipine; nicotinic acetylcholine receptors

---

Received June 26, 2003; revised September 11, 2003; accepted September 12, 2003.

This article has been cited by other articles:

				L.-Q. Ma, C. Liu, F. Wang, N. Xie, J. Gu, H. Fu, J.-H. Wang, F. Cai, J. Liu, and J.-G. Chen Activation of Phosphatidylinositol-Linked Novel D1 Dopamine Receptors Inhibits High-Voltage-Activated Ca2+ Currents in Primary Cultured Striatal Neurons J Neurophysiol, May 1, 2009; 101(5): 2230 - 2238. [Abstract] [Full Text] [PDF]

				S. D. Buckingham, A. K. Jones, L. A. Brown, and D. B. Sattelle Nicotinic Acetylcholine Receptor Signalling: Roles in Alzheimer's Disease and Amyloid Neuroprotection Pharmacol. Rev., March 1, 2009; 61(1): 39 - 61. [Abstract] [Full Text] [PDF]

				H. Sasaya, T. Utsumi, K. Shimoke, H. Nakayama, Y. Matsumura, K. Fukunaga, and T. Ikeuchi Nicotine Suppresses Tunicamycin-Induced, But Not Thapsigargin-Induced, Expression of GRP78 during ER Stress-Mediated Apoptosis in PC12 Cells J. Biochem., August 1, 2008; 144(2): 251 - 257. [Abstract] [Full Text] [PDF]

				G. F. Hedou, K. Koshibu, M. Farinelli, E. Kilic, C. E. Gee, U. Kilic, K. Baumgartel, D. M. Hermann, and I. M. Mansuy Protein Phosphatase 1-Dependent Bidirectional Synaptic Plasticity Controls Ischemic Recovery in the Adult Brain J. Neurosci., January 2, 2008; 28(1): 154 - 162. [Abstract] [Full Text] [PDF]

				T. P. Obrenovitch Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia Physiol Rev, January 1, 2008; 88(1): 211 - 247. [Abstract] [Full Text] [PDF]

				N. Kabbani, M. P. Woll, R. Levenson, J. M. Lindstrom, and J.-P. Changeux Intracellular complexes of the 2 subunit of the nicotinic acetylcholine receptor in brain identified by proteomics PNAS, December 18, 2007; 104(51): 20570 - 20575. [Abstract] [Full Text] [PDF]

				N. A. Addy, E. F. Fornasiero, T. R. Stevens, J. R. Taylor, and M. R. Picciotto Role of Calcineurin in Nicotine-Mediated Locomotor Sensitization J. Neurosci., August 8, 2007; 27(32): 8571 - 8580. [Abstract] [Full Text] [PDF]

				R. Kehat, E. Zemel, N. Cuenca, T. Evron, D. Toiber, A. Loewenstein, H. Soreq, and I. Perlman A Novel Isoform of Acetylcholinesterase Exacerbates Photoreceptors Death after Photic Stress Invest. Ophthalmol. Vis. Sci., March 1, 2007; 48(3): 1290 - 1297. [Abstract] [Full Text] [PDF]

				N. Mechawar, A. Saghatelyan, R. Grailhe, L. Scoriels, G. Gheusi, M.-M. Gabellec, P.-M. Lledo, and J.-P. Changeux Nicotinic receptors regulate the survival of newborn neurons in the adult olfactory bulb PNAS, June 29, 2004; 101(26): 9822 - 9826. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help