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, H; Mafra, RA; Chong, Y; Nicholson, GM; Beirão, PSL; Cruz, JS; Boehm, S; Nentwig, W; Kuhn-Nentwig, L

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, H Mafra, RA Chong, Y Nicholson, GM

Beirão, PSL Cruz, JS Boehm, S Nentwig, W Kuhn-Nentwig, L

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Publication Type:: Journal Article
Citation:: Neuropharmacology, 2007, 52 (8), pp. 1650 - 1662
Issue Date:: 2007-06-01

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Field	Value	Language
dc.contributor.author	Kubista, H	en_US
dc.contributor.author	Mafra, RA	en_US
dc.contributor.author	Chong, Y	en_US
dc.contributor.author	Nicholson, GM https://orcid.org/0000-0002-4277-4296	en_US
dc.contributor.author	Beirão, PSL	en_US
dc.contributor.author	Cruz, JS	en_US
dc.contributor.author	Boehm, S	en_US
dc.contributor.author	Nentwig, W	en_US
dc.contributor.author	Kuhn-Nentwig, L	en_US
dc.date.available	2007-03-21	en_US
dc.date.issued	2007-06-01	en_US
dc.identifier.citation	Neuropharmacology, 2007, 52 (8), pp. 1650 - 1662	en_US
dc.identifier.issn	0028-3908	en_US
dc.identifier.uri	http://hdl.handle.net/10453/4576
dc.description.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 C. 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. CSTX-1 blocked rat neuronal L-type, but no other types of HVA Cav channels, and failed to modulate LVA Cav channel currents. Using neuroendocrine GH3 and GH4 cells, CSTX-1 produced a rapid voltage-independent block of L-type Cav channel currents. The concentration-response curve was biphasic in GH4 neurons and the subnanomolar IC50 values were at least 1000-fold lower than in GH3 cells. L-type Cav channel currents of skeletal muscle myoballs and other voltage-gated ion currents of rat neurons, such as INa(v) or IK(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 Cav channels. © 2007 Elsevier Ltd. All rights reserved.	en_US
dc.relation.ispartof	Neuropharmacology	en_US
dc.relation.isbasedon	10.1016/j.neuropharm.2007.03.012	en_US
dc.subject.classification	Neurology & Neurosurgery	en_US
dc.subject.mesh	Ganglia, Sensory	en_US
dc.subject.mesh	Neurons	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Animals, Newborn	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Rats	en_US
dc.subject.mesh	Cockroaches	en_US
dc.subject.mesh	Nitrendipine	en_US
dc.subject.mesh	Calcium Channels, L-Type	en_US
dc.subject.mesh	Calcium Channel Blockers	en_US
dc.subject.mesh	Spider Venoms	en_US
dc.subject.mesh	Patch-Clamp Techniques	en_US
dc.subject.mesh	Electric Stimulation	en_US
dc.subject.mesh	Membrane Potentials	en_US
dc.subject.mesh	Dose-Response Relationship, Drug	en_US
dc.title	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	en_US
dc.type	Journal Article
utslib.citation.volume	8	en_US
utslib.citation.volume	52	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
utslib.for	1109 Neurosciences	en_US
utslib.for	1701 Psychology	en_US
dc.location.activity	ISI:000247864900011	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.issue	8	en_US
pubs.publication-status	Published	en_US
pubs.volume	52	en_US

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 C. 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. CSTX-1 blocked rat neuronal L-type, but no other types of HVA Cav channels, and failed to modulate LVA Cav channel currents. Using neuroendocrine GH3 and GH4 cells, CSTX-1 produced a rapid voltage-independent block of L-type Cav channel currents. The concentration-response curve was biphasic in GH4 neurons and the subnanomolar IC50 values were at least 1000-fold lower than in GH3 cells. L-type Cav channel currents of skeletal muscle myoballs and other voltage-gated ion currents of rat neurons, such as INa(v) or IK(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 Cav channels. © 2007 Elsevier Ltd. All rights reserved.

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http://hdl.handle.net/10453/4576