Thallium-sensitive fluorescent assay reveals loperamide as a new inhibitor of the potassium channel Kv10.1
Por:
Loza-Huerta, Arlet, Milo, Edgar, Picones, Arturo, Hernandez-Cruz, Arturo, Luis, Enoch
Publicada:
1 dic 2021
Ahead of Print:
1 jul 2021
Resumen:
Background Ion channels have been proposed as therapeutic targets for
different types of malignancies. One of the most studied ion channels in
cancer is the voltage-gated potassium channel ether-a-go-go 1 or Kv10.1.
Various studies have shown that Kv10.1 expression induces the
proliferation of several cancer cell lines and in vivo tumor models,
while blocking or silencing inhibits proliferation. Kv10.1 is a
promising target for drug discovery modulators that could be used in
cancer treatment. This work aimed to screen for new Kv10.1 channel
modulators using a thallium influx-based assay. Methods Pharmacological
effects of small molecules on Kv10.1 channel activity were studied using
a thallium-based fluorescent assay and patch-clamp electrophysiological
recordings, both performed in HEK293 stably expressing the human Kv10.1
potassium channel. Results In thallium-sensitive fluorescent assays, we
found that the small molecules loperamide and amitriptyline exert a
potent inhibition on the activity of the oncogenic potassium channel
Kv10.1. These results were confirmed by electrophysiological recordings,
which showed that loperamide and amitriptyline decreased the amplitude
of Kv10.1 currents in a dose-dependent manner. Both drugs could be
promising tools for further studies. Conclusions Thallium-sensitive
fluorescent assay represents a reliable methodological tool for the
primary screening of different molecules with potential activity on
Kv10.1 channels or other K+ channels.
Filiaciones:
Loza-Huerta, Arlet:
Univ Nacl Autonoma Mexico, Lab Nacl Canalopatias, Inst Fisiol Celular, Circuito Exterior S-N, Mexico City 04510, DF, Mexico
Milo, Edgar:
Univ Nacl Autonoma Mexico, Lab Nacl Canalopatias, Inst Fisiol Celular, Circuito Exterior S-N, Mexico City 04510, DF, Mexico
Picones, Arturo:
Univ Nacl Autonoma Mexico, Lab Nacl Canalopatias, Inst Fisiol Celular, Circuito Exterior S-N, Mexico City 04510, DF, Mexico
Hernandez-Cruz, Arturo:
Univ Nacl Autonoma Mexico, Lab Nacl Canalopatias, Inst Fisiol Celular, Circuito Exterior S-N, Mexico City 04510, DF, Mexico
Univ Nacl Autonoma Mexico, Dept Neurociencia Cognit, Inst Fisiol Celular, Circuito Exterior S-N, Mexico City 04510, DF, Mexico
Luis, Enoch:
Univ Nacl Autonoma Mexico, Lab Nacl Canalopatias, Inst Fisiol Celular, Circuito Exterior S-N, Mexico City 04510, DF, Mexico
Univ Nacl Autonoma Mexico, Catedras CONACYT Inst Fisiol Celular, Circuito Exterior S-N, Mexico City 04510, DF, Mexico
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