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Inhibition of Neuronal Calcium Channels by a Novel Peptide Spider Toxin, DW13.3
Peptide toxins have proved to be useful agents, both in discriminating between different components of native calcium channel currents and in the molecular isolation and designation of their cloned channel counterparts. Here, we describe the isolation and characterization of the biochemical and phys...
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Published in: | Molecular pharmacology 1998-08, Vol.54 (2), p.407-418 |
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Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Peptide toxins have proved to be useful agents, both in discriminating between different components of native calcium channel
currents and in the molecular isolation and designation of their cloned channel counterparts. Here, we describe the isolation
and characterization of the biochemical and physiological properties of a novel 74-amino acid peptide toxin (DW13.3) extracted
from the venom of the spider Filistata hibernalis . The subtype specificity of DW13.3 was investigated using calcium channel currents recorded from two separate expression
systems and several different cultured mammalian cell preparations. Overall, DW13.3 potently blocked all native calcium channel
currents studied, with the exception of T-type currents recorded from GH3 cells. Examination of transiently expressed calcium
channels in oocytes showed that DW13.3 had the highest affinity for α1A, followed by α1B > α1C > α1E. The affinity of DW13.3
for α1B N-type currents varied by 10-fold between expressed channels and native currents. Although block occurred in a similar
1:1 manner for all subtypes, DW13.3 produced a partial block of both α1A currents and P-type currents in cerebellar Purkinje
cells. Selective occlusion of the P/Q-type channel ligand Ï-conotoxin MVIIC (but not Ï-agatoxin IVA) from its binding site
in Purkinje neurons suggests that DW13.3 binds to a site close to the pore of the channel. The inhibition of different subtypes
of calcium channels by DW13.3 reflects a common âmacroâ binding site present on all calcium channels except T-type. |
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ISSN: | 0026-895X 1521-0111 |
DOI: | 10.1124/mol.54.2.407 |