For submission to Neuropharmacology CSTX-1, a toxin from the venom of the hunting spider Cupiennius salei, is a selective blocker of L-type calcium channels in mammalian neurons *,1Helmut Kubista, 2Roberta A. Mafra, 3Youmie Chong, 3Graham M. Nicholson, 2Paulo S.L. Beirão, 2Jader S. Cruz, 4Stefan Boehm, 5Wolfgang Nentwig & 5Lucia Kuhn-Nentwig 1Center for Biomolecular Medicine and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Waehringerstrasse 13a, A-1090, Vienna, Austria 2Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil 3Neurotoxin Research Group, Department of Medical & Molecular Biosciences, University of Technology, Sydney, City Campus, Broadway, Sydney, NSW 2007, Australia 4Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, A-8010 Graz, Austria 5Zoological Institute, University of Bern, Baltzerstrasse 6, CH-3012 Bern, Switzerland *Author for correspondence: Telephone: ++43 1 4277 64146 Fax: ++ 43 1 4277 9641 E-mail:
[email protected] H. Kubista et al. CSTX-1, a selective Cav channel blocker 2 Abstract The inhibitor cystine-knot motif identified in the structure of CSTX-1 from Cupiennius salei venom suggests that this toxin may act as a blocker of ion channels. Whole-cell patch clamp experiments performed on cockroach neurons revealed that CSTX-1 produced a slow voltage- independent block of both mid/low- (M-LVA) and high-voltage-activated (HVA) insect Cav channels. Since Cupiennius salei venom affects both insect as well as rodent species, we investigated whether Cav channel currents of rat neurons are also inhibited by CSTX-1.