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

Kubista, Helmut; Mafra, Roberta; Chong, Youmie; Nicholson, Graham; Beirao, Paulo; Cruz, Jader; Boehm, Stefan; Nentwig, Wolfgang; Kuhn-Nentwig, Lucia (2007). 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. Neuropharmacology, 8(52), pp. 1650-1662. Orlando, Fla.: Elsevier 10.1016/j.neuropharm.2007.03.012

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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 Ca(v) channels. Since C. salei venom affects both insect as well as rodent species, we investigated whether Ca(v) channel currents of rat neurons are also inhibited by CSTX-1. CSTX-1 blocked rat neuronal L-type, but no other types of HVA Ca(v) channels, and failed to modulate LVA Ca(v) channel currents. Using neuroendocrine GH3 and GH4 cells, CSTX-1 produced a rapid voltage-independent block of L-type Ca(v) channel currents. The concentration-response curve was biphasic in GH4 neurons and the subnanomolar IC(50) values were at least 1000-fold lower than in GH3 cells. L-type Ca(v) channel currents of skeletal muscle myoballs and other voltage-gated ion currents of rat neurons, such as I(Na(v)) or I(K(v)) were not affected by CSTX-1. The high potency and selectivity of CSTX-1 for a subset of L-type channels in mammalian neurons may enable the toxin to be used as a molecular tool for the investigation of this family of Ca(v) channels.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Ecology and Evolution (IEE) > Community Ecology

UniBE Contributor:

Nentwig, Wolfgang and Kuhn-Nentwig, Lucia

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 590 Animals (Zoology)
500 Science > 580 Plants (Botany)

ISSN:

0028-3908

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:58

Last Modified:

24 Mar 2014 04:06

Publisher DOI:

10.1016/j.neuropharm.2007.03.012

PubMed ID:

17517422

Web of Science ID:

000247864900011

URI:

https://boris.unibe.ch/id/eprint/24798 (FactScience: 52962)

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