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Subtype specificity interaction of bactridines with mammalian, insect and bacterial sodium channels under voltage clamp conditions
Author(s) -
Peigneur Steve,
Sevcik Carlos,
Tytgat Jan,
Castillo Cecilia,
D'Suze Gina
Publication year - 2012
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2012.08808.x
Subject(s) - sodium channel , clamp , voltage clamp , insect , patch clamp , biophysics , biology , sodium , ion channel , chemistry , electrophysiology , biochemistry , membrane potential , ecology , neuroscience , computer science , receptor , organic chemistry , clamping , computer vision
The present work demonstrates that bactridines ( B acts) possess different selectivities for neuronal and muscular voltage‐dependent sodium ( N a V ) channels, with subtle differences on channel isoforms. Bacts 2, 3, 4, 5 and 6 (100 n m ) reduced the peak current of several skeletal and neuronal channel isoforms selectively. Bacts 2 and 3 were more potent on N a V 1.4, Bacts 4 and 6 on N a V 1.3 and B act 5 on N a V 1.7. Bactridines (except B acts 1 and 5) caused a hyperpolarizing shift in the V 1/2 of activation and inactivation of N a V 1.3, Na V 1.4 and N a V 1.6. Voltage shifts of B oltzmann curves fitted to activation and inactivation occurred with a decrease in κ. Since the slope is proportional to κ = RT / zF , changes in κ 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 N a V 1.2 IFM / QQQ ; peak I N a was reduced in both channel forms, suggesting that channel blockage resulted from toxin binding to a site partially distinct from the α subunit binding site 4. Bactridines emerge as potential research tools to understand sodium channel isoform structure–function relationships and also as pharmacologically interesting peptides.