Key result
Extracellular acidosis (pH 6.3) significantly increased the IC50 values for hERG channel inhibition by flecainide and dofetilide, but not amiodarone, compared to pH 7.4.
Population
hERG-expressing Human Embryonic Kidney (HEK293) cells
Comparison
Extracellular acidosis and intracellular… vs Normal pH (external pH 7.4, pipette pH 7.2)
Design
Preclinical
Authors
Loading...
May attenuate flecainide/dofetilide effects in ischemia; hypothesis-generating for pH-dependent dosing, needs clinical validation.
Extracellular, but not intracellular, acidosis reduces the hERG blocking potency of dofetilide and flecainide, potentially contributing to heterogeneous drug effects during ischemia.
Du et al. (2011) studied this question. Extracellular and intracellular acidosis (pH 6.3) with dofetilide, flecainide, and amiodarone vs. Normal pH (7.4) was evaluated on Half-maximal inhibitory concentration (IC50) values for IhERG tail inhibition. Extracellular acidosis (pH 6.3) significantly increased the IC50 values for hERG channel inhibition by flecainide and dofetilide, but not amiodarone, compared to pH 7.4.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: