期刊
FEBS JOURNAL
卷 279, 期 21, 页码 4025-4038出版社
WILEY
DOI: 10.1111/j.1742-4658.2012.08808.x
关键词
bactridines; NaV channels; scorpion; sequence; Tityus discrepans
资金
- Venezuelan FONACIT [S1-2001000908]
- FONDEN [416]
- Mision Ciencia [200700642]
- F.W.O. Vlaanderen [G.0433.12]
- Inter-University Attraction Poles Program, Belgian State, Belgian Science Policy [IUAP 7/19]
- KU Leuven [OT/12/081]
The present work demonstrates that bactridines (Bacts) possess different selectivities for neuronal and muscular voltage-dependent sodium (NaV) channels, with subtle differences on channel isoforms. Bacts 2, 3, 4, 5 and 6 (100 nm) reduced the peak current of several skeletal and neuronal channel isoforms selectively. Bacts 2 and 3 were more potent on Na(V)1.4, Bacts 4 and 6 on Na(V)1.3 and Bact 5 on Na(V)1.7. Bactridines (except Bacts 1 and 5) caused a hyperpolarizing shift in the V(1/)2 of activation and inactivation of Na(V)1.3, Na(V)1.4 and NaV1.6. Voltage shifts of Boltzmann curves fitted to activation and inactivation occurred with a decrease in kappa. Since the slope is proportional to kappa = RT/zF, changes in kappa probably express changes in z, the valence, in a voltage-dependent manner. Changes in z may express toxin-induced changes in the channel ionic environment, perhaps due to surface charges of the molecules. Bact 2 induced a Na(V)1.2 voltage shift of the activation curves but no shift of the mutant Na(V)1.2 IFM/QQQ; peak I-Na was reduced in both channel forms, suggesting that channel blockage resulted from toxin binding to a site partially distinct from the a subunit binding site 4. Bactridines emerge as potential research tools to understand sodium channel isoform structurefunction relationships and also as pharmacologically interesting peptides.
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