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Originally published In Press as doi:10.1074/jbc.M209969200 on November 18, 2002

J. Biol. Chem., Vol. 278, Issue 6, 4057-4062, February 7, 2003
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omega -Conotoxin CVID Inhibits a Pharmacologically Distinct Voltage-sensitive Calcium Channel Associated with Transmitter Release from Preganglionic Nerve Terminals*

David J. AdamsDagger §, Amanda B. SmithDagger , Christina I. SchroederDagger , Takahiro YasudaDagger , and Richard J. LewisDagger

From the Dagger  School of Biomedical Sciences and  Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia

Neurotransmitter release from preganglionic parasympathetic neurons is resistant to inhibition by selective antagonists of L-, N-, P/Q-, R-, and T-type calcium channels. In this study, the effects of different omega -conotoxins from genus Conus were investigated on current flow-through cloned voltage-sensitive calcium channels expressed in Xenopus oocytes and nerve-evoked transmitter release from the intact preganglionic cholinergic nerves innervating the rat submandibular ganglia. Our results indicate that omega -conotoxin CVID from Conus catus inhibits a pharmacologically distinct voltage-sensitive calcium channel involved in neurotransmitter release, whereas omega -conotoxin MVIIA had no effect. omega -Conotoxin CVID and MVIIA inhibited depolarization-activated Ba2+ currents recorded from oocytes expressing N-type but not L- or R-type calcium channels. High affinity inhibition of the CVID-sensitive calcium channel was enhanced when position 10 of the omega -conotoxin was occupied by the smaller residue lysine as found in CVID instead of an arginine as found in MVIIA. Given that relatively small differences in the sequence of the N-type calcium channel alpha 1B subunit can influence omega -conotoxin access (Feng, Z. P., Hamid, J., Doering, C., Bosey, G. M., Snutch, T. P., and Zamponi, G. W. (2001) J. Biol. Chem. 276, 15728-15735), it is likely that the calcium channel in preganglionic nerve terminals targeted by CVID is a N-type (Cav2.2) calcium channel variant.

* This work was supported in part by the Australian Research Council and National Health and Medical Research Council of Australia.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ To whom correspondence should be addressed: School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia. Tel.: 61-7-3365-1074; Fax: 61-7-3365-4933; E-mail: dadams@mailbox.uq.edu.au.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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