Format

Send to

Choose Destination
Brain Res. 2017 May 15;1663:87-94. doi: 10.1016/j.brainres.2017.03.009. Epub 2017 Mar 11.

Inhibition of Kir4.1 potassium channels by quinacrine.

Author information

1
Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, Col 28045, Mexico.
2
CONACYT, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, SLP 78210, Mexico.
3
Department of Physiology and Biophysics, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA.
4
Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, Col 28045, Mexico. Electronic address: tania@ucol.mx.
5
Departamento de Fisiología y Biofísica, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, SLP 78210, Mexico. Electronic address: aldo.rodriguez@uaslp.mx.

Abstract

Inwardly rectifying potassium (Kir) channels are expressed in many cell types and contribute to a wide range of physiological processes. Particularly, Kir4.1 channels are involved in the astroglial spatial potassium buffering. In this work, we examined the effects of the cationic amphiphilic drug quinacrine on Kir4.1 channels heterologously expressed in HEK293 cells, employing the patch clamp technique. Quinacrine inhibited the currents of Kir4.1 channels in a concentration and voltage dependent manner. In inside-out patches, quinacrine inhibited Kir4.1 channels with an IC50 value of 1.8±0.3μM and with extremely slow blocking and unblocking kinetics. Molecular modeling combined with mutagenesis studies suggested that quinacrine blocks Kir4.1 by plugging the central cavity of the channels, stabilized by the residues E158 and T128. Overall, this study shows that quinacrine blocks Kir4.1 channels, which would be expected to impact the potassium transport in several tissues.

KEYWORDS:

Cationic amphiphilic drugs; Kir4.1 channels; Quinacrine

PMID:
28288868
PMCID:
PMC5502112
DOI:
10.1016/j.brainres.2017.03.009
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center