期刊
FEBS JOURNAL
卷 277, 期 4, 页码 918-930出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1742-4658.2009.07533.x
关键词
channel isoforms; ion channels; sodium channel inactivation; toxin binding; wasp toxins
资金
- Italian Ministero dell'Universita e della Ricerca Scientifica e Tecnologica [MIUR-PRIN2005-2001055320, MIUR-FIRB2001-RBNE01XMP4-002, MIUR-FISR2001-0300179, MIU-PRIN2003-2005]
- Universita di Milano-Bicocca
- F.W.O. Vlaanderen [G.0330.06, G.0257.08]
- Interuniversity Attraction Poles Program-Belgian State-Belgian Science Policy [UAP p6/31]
- Wetenschappelijk Onderzoek Multiple Sclerose
Pompilidotoxins (PMTXs, alpha and beta) are small peptides consisting of 13 amino acids purified from the venom of the solitary wasps Anoplius samariensis (alpha-PMTX) and Batozonellus maculifrons (beta-PMTX). They are known to facilitate synaptic transmission in the lobster neuromuscular junction, and to slow sodium channel inactivation. By using beta-PMTX, alpha-PMTX and four synthetic analogs with amino acid changes, we conducted a thorough study of the effects of PMTXs on sodium current inactivation in seven mammalian voltage-gated sodium channel (VGSC) isoforms and one insect VGSC (DmNa(v)1). By evaluating three components of which the inactivating current is composed (fast, slow and steady-state components), we could distinguish three distinct groups of PMTX effects. The first group concerned the insect and Na(v)1.6 channels, which showed a large increase in the steady-state current component without any increase in the slow component. Moreover, the dose-dependent increase in this steady-state component was correlated with the dose-dependent decrease in the fast component. A second group of effects concerned the Na(v)1.1, Na(v)1.2, Na(v)1.3 and Na(v)1.7 isoforms, which responded with a large increase in the slow component, and showed only a small steady-state component. As with the first group of effects, the slow component was dose-dependent and correlated with the decrease in the fast component. Finally, a third group of effects concerned Na(v)1.4 and Na(v)1.5, which did not show any change in the slow or steady-state component. These data shed light on the complex and intriguing behavior of VGSCs in response to PMTXs, helping us to better understand the molecular determinants explaining isoform-specific effects.
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