Referenced in: none

Automatically associated channels: Slo1

Title: Subtype specificity interaction of bactridines with mammalian, insect and bacterial sodium channels under voltage clamp conditions.

Authors: Steve Peigneur, Carlos Sevcik, Jan Tytgat, Cecilia Castillo, Gina D'Suze

Journal, date & volume: FEBS J., 2012 Nov , 279, 4025-38

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22925163

Abstract
The present work demonstrates that bactridines (Bacts) possess different selectivities for neuronal and muscular voltage-dependent sodium (Na(V) ) 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 Na(V) 1.6. Voltage shifts of Boltzmann 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 Na(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.