HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 17/2/221    most recent 00202.2003v1 Alert me when this article is cited 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 (18) Citing Articles via Google Scholar Google Scholar Articles by Kedmi, M. Articles by Orr-Urtreger, A. Search for Related Content PubMed PubMed Citation Articles by Kedmi, M. Articles by Orr-Urtreger, A.

Mice lacking neuronal nicotinic acetylcholine receptor ß4-subunit and mice lacking both 5- and ß4-subunits are highly resistant to nicotine-induced seizures

¹ Genetic Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
² Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030

Nicotine, the main addictive component of tobacco, evokes a wide range of dose-dependent behaviors in rodents, and when administrated in high doses, it can induce clonic-tonic seizures. Nicotine acts through the nicotinic acetylcholine receptors (nAChRs). Mutations in the human 4- and the ß2-nAChR subunit genes cause autosomal dominant nocturnal frontal lobe epilepsy. Using transgenic mice with mutations in nAChR subunits, it was demonstrated previously that the 4-, 5-, and 7-subunits are involved in nicotine-induced seizures. To examine the possibility that the ß4-subunit is also involved in this phenotype, we tested mice with homozygous ß4-subunit deficiency. The ß4 null mice were remarkably resistant to nicotine-induced seizures compared with wild-type and 5 null mice. We also generated mice with double deficiency of both 5- and ß4-nAChR subunits and demonstrated that they were more resistant to nicotine’s convulsant effect than either the 5 or the ß4 single mutant mice. In addition, the single 5 mutants and the double 5ß4-deficient mice exhibited a significantly shorter latency time to seizure than that of the wild-type mice. Our results thus show that ß4-containing nAChRs have a crucial role in the pathogenesis of nicotine-induced seizures. Furthermore, by comparing multiple mutant mice with single and double subunit deficiency, we suggest that nicotinic receptors containing either 5- or ß4-subunits are involved in nicotine-induced seizures and that receptors containing both subunits are likely to contribute to this phenomena as well. However, the 5-subunit, but not the ß4-subunit, regulates the rate of response to high doses of nicotine.

neuronal nicotinic acetylcholine receptor 5- and ß4-subunits; knockout mice

This article has been cited by other articles:

				A. Kuryatov, J. Onksen, and J. Lindstrom Roles of Accessory Subunits in {alpha}4{beta}2* Nicotinic Receptors Mol. Pharmacol., July 1, 2008; 74(1): 132 - 143. [Abstract] [Full Text] [PDF]

				Y. Teper, D. Whyte, E. Cahir, H. A. Lester, S. R. Grady, M. J. Marks, B. N. Cohen, C. Fonck, T. McClure-Begley, J. M. McIntosh, et al. Nicotine-Induced Dystonic Arousal Complex in a Mouse Line Harboring a Human Autosomal-Dominant Nocturnal Frontal Lobe Epilepsy Mutation J. Neurosci., September 19, 2007; 27(38): 10128 - 10142. [Abstract] [Full Text] [PDF]

				M. Kedmi and A. Orr-Urtreger Expression changes in mouse brains following nicotine-induced seizures: the modulation of transcription factor networks Physiol Genomics, August 20, 2007; 30(3): 242 - 252. [Abstract] [Full Text] [PDF]

				M. Kedmi and A. Orr-Urtreger Differential brain transcriptome of {beta}4 nAChR subunit-deficient mice: is it the effect of the null mutation or the background strain? Physiol Genomics, January 17, 2007; 28(2): 213 - 222. [Abstract] [Full Text] [PDF]

				J. Wu, Q. Liu, K. Yu, J. Hu, Y.-P. Kuo, M. Segerberg, P. A. St John, and R. J. Lukas Roles of nicotinic acetylcholine receptor {beta} subunits in function of human {alpha}4-containing nicotinic receptors J. Physiol., October 1, 2006; 576(1): 103 - 118. [Abstract] [Full Text] [PDF]

				C. Fonck, B. N. Cohen, R. Nashmi, P. Whiteaker, D. A. Wagenaar, N. Rodrigues-Pinguet, P. Deshpande, S. McKinney, S. Kwoh, J. Munoz, et al. Novel Seizure Phenotype and Sleep Disruptions in Knock-In Mice with Hypersensitive {alpha}4* Nicotinic Receptors J. Neurosci., December 7, 2005; 25(49): 11396 - 11411. [Abstract] [Full Text] [PDF]

				H. Fischer, A. Orr-Urtreger, L. W Role, and S. Huck Selective deletion of the {alpha}5 subunit differentially affects somatic-dendritic versus axonally targeted nicotinic ACh receptors in mouse J. Physiol., February 15, 2005; 563(1): 119 - 137. [Abstract] [Full Text] [PDF]

				R. Salas, F. Pieri, and M. De Biasi Decreased Signs of Nicotine Withdrawal in Mice Null for the {beta}4 Nicotinic Acetylcholine Receptor Subunit J. Neurosci., November 10, 2004; 24(45): 10035 - 10039. [Abstract] [Full Text] [PDF]