Mibefradil, a T-type Ca²⁺ channel blocker also blocks Orai channels by action at the extracellular surface.

ABSTRACT:

Background and purpose

Mibefradil, a T-type Ca²⁺ channel blocker, has been investigated for treating solid tumours. However, its underlying mechanisms are still unclear. Here, we have investigated the pharmacological actions of mibefradil on Orai store-operated Ca²⁺ channels.

Experimental approach

Human Orai1-3 cDNAs in tetracycline-regulated pcDNA4/TO vectors were transfected into HEK293 T-REx cells with stromal interaction molecule 1 (STIM1) stable expression. The Orai currents were recorded by whole-cell and excised-membrane patch clamp. Ca²⁺ influx or release was measured by Fura-PE3/AM. Cell growth and death were monitored by WST-1, LDH assays and flow cytometry.

Key results

Mibefradil inhibited Orai1, Orai2, and Orai3 currents do

SUBMITTER: Li P 

PROVIDER: S-EPMC6780027 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature