title: Inhibition of Kir4.1 potassium channels by quinacrine.
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.
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, Col 28045, Mexico.
authors.forename: Leticia G
authors.initials: LG
authors.lastname: Marmolejo-Murillo
authors.affiliation: CONACYT, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, SLP 78210, Mexico.
authors.forename: Iván A
authors.initials: IA
authors.lastname: Aréchiga-Figueroa
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Cui
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, Col 28045, Mexico.
authors.forename: Eloy G
authors.initials: EG
authors.lastname: Moreno-Galindo
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, Col 28045, Mexico.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Navarro-Polanco
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, Col 28045, Mexico.
authors.forename: José A
authors.initials: JA
authors.lastname: Sánchez-Chapula
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, Col 28045, Mexico. Electronic address: tania@ucol.mx.
authors.forename: Tania
authors.initials: T
authors.lastname: Ferrer
authors.affiliation: Departamento de Fisiología y Biofísica, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, SLP 78210, Mexico. Electronic address: aldo.rodriguez@uaslp.mx.
authors.forename: Aldo A
authors.initials: AA
authors.lastname: Rodríguez-Menchaca
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism*; D011796:Quinacrine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats
chemical_list: D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011796:Quinacrine; D011188:Potassium
keywords: Cationic amphiphilic drugs; Kir4.1 channels; Quinacrine