Sigma non-opioid receptor 1 is a potential therapeutic target for long QT syndrome.

ABSTRACT: Some missense gain-of-function mutations in CACNA1C gene, encoding calcium channel Ca_V1.2, cause a life-threatening form of long QT syndrome named Timothy syndrome, with currently no clinically-effective therapeutics. Here we report that pharmacological targeting of sigma non-opioid intracellular receptor 1 (SIGMAR1) can restore electrophysiological function in iPSC-derived cardiomyocytes generated from patients with Timothy syndrome and two common forms of long QT syndrome, type 1 (LQTS1) and 2 (LQTS2), caused by missense trafficking mutations in potassium channels. Electrophysiological recordings demonstrate that an FDA-approved cough suppressant, dextromethorphan, can be used as an agonist of SIGMAR1, to shorten the prolonged action potential in Timothy syndrome cardio

SUBMITTER: Song L 

PROVIDER: S-EPMC9431959 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature