Identification of a PEST Sequence in Vertebrate K2.1 That Modifies Rectification.

K2.1 potassium channels, producing inward rectifier potassium current ( ), are important for final action potential repolarization and a stable resting membrane potential in excitable cells like cardiomyocytes. Abnormal K2.

PA-6 inhibits inward rectifier currents carried by V93I and D172N gain-of-function K2.1 channels, but increases channel protein expression.

Background: The inward rectifier potassium current I contributes to a stable resting membrane potential and phase 3 repolarization of the cardiac action potential. KCNJ2 gain-of-function mutations V93I and D172N associate with increased I, short QT syndrome type 3 and congenital atrial fibrillation. Pentamidine-Analogue 6 (PA-6) is an efficient (IC = 14 nM with inside-out patch clamp methodology) and specific I inhibitor that interacts with the cytoplasmic pore region of the K2.