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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. 2007 Jun; 52(8):1650-62.N

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 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.

Authors+Show Affiliations

Center for Biomolecular Medicine and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Waehringerstrasse 13a, A-1090 Vienna, Austria. helmut.kubista@meduniwien.ac.atNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17517422

Citation

Kubista, Helmut, et al. "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, vol. 52, no. 8, 2007, pp. 1650-62.
Kubista H, Mafra RA, Chong Y, et al. 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. 2007;52(8):1650-62.
Kubista, H., Mafra, R. A., Chong, Y., Nicholson, G. M., Beirão, P. S., Cruz, J. S., Boehm, S., Nentwig, W., & Kuhn-Nentwig, L. (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, 52(8), 1650-62.
Kubista H, et al. 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. 2007;52(8):1650-62. PubMed PMID: 17517422.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Kubista,Helmut, AU - Mafra,Roberta A, AU - Chong,Youmie, AU - Nicholson,Graham M, AU - Beirão,Paulo S L, AU - Cruz,Jader S, AU - Boehm,Stefan, AU - Nentwig,Wolfgang, AU - Kuhn-Nentwig,Lucia, Y1 - 2007/04/04/ PY - 2006/09/14/received PY - 2007/02/28/revised PY - 2007/03/21/accepted PY - 2007/5/23/pubmed PY - 2007/10/27/medline PY - 2007/5/23/entrez SP - 1650 EP - 62 JF - Neuropharmacology JO - Neuropharmacology VL - 52 IS - 8 N2 - 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. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/17517422/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(07)00092-5 DB - PRIME DP - Unbound Medicine ER -