Methadone Blockade of Cardiac Inward Rectifier K⁺ Current Augments Membrane Instability and Amplifies U Waves on Surface ECGs: A Translational Study.

ABSTRACT: Background Methadone is associated with a disproportionate risk of sudden death and ventricular tachyarrhythmia despite only modest inhibition of delayed rectifier K⁺ current (I_Kr)_, the principal mechanism of drug-associated arrhythmia. Congenital defects of inward rectifier K⁺ current (I_K1) have been linked to increased U-wave amplitude on ECG and fatal arrhythmia. We hypothesized that methadone may also be a potent inhibitor of I_K1, contributing to delayed repolarization and manifesting on surface ECGs as augmented U-wave integrals. Methods and Results Using a whole-cell voltage clamp, methadone inhibited both recombinant and native I_K1 with a half-maximal inhibitory concentration IC5

SUBMITTER: Klein MG 

PROVIDER: S-EPMC9238736 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature