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

Publication Type:
Journal Article
Citation:
Neuropharmacology, 2007, 52 (8), pp. 1650 - 1662
Issue Date:
2007-06-01
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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 Cavchannels. Since C. salei venom affects both insect as well as rodent species, we investigated whether Cavchannel currents of rat neurons are also inhibited by CSTX-1. CSTX-1 blocked rat neuronal L-type, but no other types of HVA Cavchannels, and failed to modulate LVA Cavchannel currents. Using neuroendocrine GH3 and GH4 cells, CSTX-1 produced a rapid voltage-independent block of L-type Cavchannel currents. The concentration-response curve was biphasic in GH4 neurons and the subnanomolar IC50values were at least 1000-fold lower than in GH3 cells. L-type Cavchannel 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 Cavchannels. © 2007 Elsevier Ltd. All rights reserved.
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