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.
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.
Kubista
Helmut
H
Center for Biomolecular Medicine and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Waehringerstrasse 13a, A-1090 Vienna, Austria. helmut.kubista@meduniwien.ac.at
Mafra
Roberta A
RA
Chong
Youmie
Y
Nicholson
Graham M
GM
Beirão
Paulo S L
PS
Cruz
Jader S
JS
Boehm
Stefan
S
Nentwig
Wolfgang
W
Kuhn-Nentwig
Lucia
L
D000818:Animals; D000831:Animals, Newborn; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000502:physiology*; D002478:Cells, Cultured; D003058:Cockroaches / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D017950:Ganglia, Sensory / Q000166:cytology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D009568:Nitrendipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D013111:Spider Venoms / Q000737:chemistry* / Q000494:pharmacology*
C523732:CSTX-1, Cupiennius salei; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D013111:Spider Venoms; D009568:Nitrendipine