In vitro and in silico characterization of the inhibition of Kir4.1 channels by aminoglycoside antibiotics.

ABSTRACT:

Background and purpose

Aminoglycoside antibiotics are positively charged molecules that are known to inhibit several ion channels. In this study, we have shown that aminoglycosides also inhibit the activity of Kir4.1 channels. Aminoglycosides inhibit Kir4.1 channels by a pore-blocking mechanism, plugging the central vestibule of the channel.

Experimental approach

Patch-clamp recordings were made in HEK-293 cells transiently expressing Kir4.1 channels to analyse the effects of gentamicin, neomycin and kanamycin. In silico modelling followed by mutagenesis were realized to identify the residues critical for aminoglycosides binding to Kir4.1.

Key results

Aminoglycoside antibiotics block Kir4.1 channels in a concentration- and voltage-dependent manner, getting access to t

SUBMITTER: Moran-Zendejas R 

PROVIDER: S-EPMC7484562 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature