Abstract
Animal toxins that inhibit voltage-gated sodium (Na(v)) channel fast inactivation can do so through an interaction with the S3b-S4 helix-turn-helix region, or paddle motif, located in the domain IV voltage sensor. Here, we used surface plasmon resonance (SPR), an optical approach that uses polarized light to measure the refractive index near a sensor surface to which a molecule of interest is attached, to analyze interactions between the isolated domain IV paddle and Na(v) channel-selective α-scorpion toxins. Our SPR analyses showed that the domain IV paddle can be removed from the Na(v) channel and immobilized on sensor chips, and suggest that the isolated motif remains susceptible to animal toxins that target the domain IV voltage sensor. As such, our results uncover the inherent pharmacological sensitivities of the isolated domain IV paddle motif, which may be exploited to develop a label-free SPR approach for discovering ligands that target this region.