Interaction of SNX482 with Domains III and IV Inhibits Activation Gating of α1E (CaV2.3) Calcium Channels
By E. Bourinet, S. Stotz, R. Spaetgens, G. Dayanithi, J. Lemos, J. Nargeot, G. Zamponi. 2001
126 citations recorded by the source corpus.
We have investigated the action of SNX482, a toxin isolated from the venom of the tarantula Hysterocrates gigas, on voltage-dependent calcium channels expressed in tsa-201 cells. Upon application of 200 nM SNX482, R-type alpha(1E) calcium channels underwent rapid and complete inhibition, which was only poorly reversible upon washout. However, upon application of strong membrane depolarizations, rapid and complete recovery from inhibition was obtained. Tail current analysis revealed that SNX482 mediated an approximately 70 mV depolarizing shift in half-activation potential, suggesting that the toxin inhibits alpha(1E) calcium channels by preventing their activation. Experiments involving chimeric channels combining structural features of alpha(1E) and alpha(1C) subunits indicated that the presence of the domain III and IV of alpha(1E) is a prerequisite for a strong gating inhibition. In contrast, L-type alpha(1C) channels underwent incomplete inhibition at saturating concentrations of SNX482 that was paralleled by a small shift in half-activation potential and which could be rapidly reversed, suggesting a less pronounced effect of the toxin on L-type calcium channel gating. We conclude that SNX482 does not exhibit unequivocal specificity for R-type channels, but highly effectively antagonizes their activation.
Subfields: Cardiology and Cardiovascular Medicine, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/e2acb634c8692dd640b8cea76c67e83ff375283f
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In Cardiology and Cardiovascular Medicine
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Citations in the corpus
- The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential (2015, background): “Although most typically thought of as blockers of LTCCs, there is evidence that someDHPs can also block N-type calcium channels with high affinity.”
- Neuronal voltage-gated calcium channels: structure, function, and dysfunction. (2014, background): “3 corresponds to R-type channels (Soong et al., 1993) that can be inhibited by SNX-482, a peptide from Hyristocrates Gigas Tarantula venom (Bourinet et al., 2001; Newcomb et al., HVA channels are heteromultimers comprised of a pore-forming Cava1 subunit that coassembles with ancillary Cavb, Cava2d,…”