Molecular mechanism of the spider toxin κ-LhTx-I acting on the bacterial voltage-gated sodium channel NaChBac.

ABSTRACT: The bacterial sodium channel NaChBac is the prokaryotic prototype for the eukaryotic Na_V and Ca_V channels, which could be used as a relatively simple model to study their structure-function relationships. However, few modulators of NaChBac have been reported thus far, and the pharmacology of NaChBac remains to be investigated. In the present study, we show that the spider toxin κ-LhTx-1, an antagonist of the K_V4 family potassium channels, potently inhibits NaChBac with an IC₅₀ of 491.0 ± 61.7 nM. Kinetics analysis revealed that κ-LhTx-1 inhibits NaChBac by impeding the voltage-sensor activation. Site-directed mutagenesis confirmed that phenylalanine-103 (F103) in the S3-S4 extracellular loop of NaChBac was critical for interacting with κ-LhTx-1.

SUBMITTER: Xiao Z 

PROVIDER: S-EPMC9386039 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature