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This Article Full Text Full Text (PDF) All Versions of this Article: 563/1/119    most recent jphysiol.2004.075788v1 Services Email this article to a friend Similar articles in this journal 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 Google Scholar Google Scholar Articles by Fischer, H. Articles by Huck, S. Search for Related Content PubMed PubMed Citation Articles by Fischer, H. Articles by Huck, S.

¹ Division of Biochemistry and Molecular Biology, Centre for Brain Research, Medical University Vienna, Spitalgasse 4, A-1090 Vienna, Austria
² The Genetic Institute, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, 6 Weizmann Street, Tel Aviv 64239, Israel
³ Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, 722 West 168th Street, Research Annex Room 807, New York, NY 10032, USA

We have compared the functional properties of nicotinic acetylcholine receptors (nAChRs) within both somatic and presynaptic domains of superior cervical ganglion (SCG) neurones from wild-type (WT) mice with those expressed by SCG neurones from mice with a targeted deletion of the gene for the 5-subunit. The functional profile of somatic nAChRs was assayed by direct macroscopic current recording and from measurements of nicotinic agonist-induced calcium transients with fura-2 imaging. The profile of nAChRs at presynaptic sites was assayed by measurement of nicotinic agonist-induced transmitter release (as preloaded [³H]noradrenaline) under conditions of action potential blockade. We have examined the responses to the nicotinic agonists acetylcholine, nicotine, cytisine, dimethylphenylpiperazinium iodide (DMPP) and epibatidine. Macroscopic current and calcium imaging assays revealed several differences in the functional profile of somatic nAChRs in WT SCG neurones compared with those from mice with the 5 subunit deleted. Somatic nAChRs in control animals were more potently activated by cytisine as compared to DMPP. In contrast, DMPP was consistently more potent than cytisine in mice lacking the 5 nAChR subunit. Differences in the somatic nAChR rank order of potency were most prominent after a least 1 day in vitro. The magnitude of somatic nAChR responses to nicotinic agonists was not substantially different in control mice compared with those of 5 subunit-deleted animals. Comparison of presynaptic nAChR-mediated responses in WT versus 5 subunit-deleted animals revealed a very different set of changes in the functional profile of prejunctional nAChRs compared with somatic nAChRs. In contrast to somatic nAChRs, the responses of prejunctional receptors were markedly enhanced in 5 knockout animals compared with control. Furthermore, all prejunctional receptor responses were most potently activated by DMPP in both control and in 5 subunit-deleted mice. Hence, the presence or absence of the 5 subunit did not affect the rank order of potency of agonists at preterminal sites but greatly affected the magnitude of presynaptic nAChR-mediated responses. The enhanced efficacy of nicotine at presynaptic receptors was corroborated in an acute atrium preparation from postnatal 5 subunit-deleted mice. These results confirm and significantly extend our previous observation that in the sympathetic nervous system, somatic and prejunctional receptors are different and rely on the presence of the 5 subunit in a distinct manner.

(Received 22 September 2004; accepted after revision 14 December 2004; first published online 20 December 2004)
Corresponding author S. Huck: Division of Biochemistry and Molecular Biology, Centre for Brain Research, Medical University Vienna, Spitalgasse 4, A-1090 Vienna, Austria. Email: sigismund.huck{at}meduniwien.ac.at

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