Potassium (K+) channels are categorized by their mode of activation and the number of transmembrane segments. The voltage-gated six-transmembrane K+ channels include KCNQ1, first recognized for its role in cardiac function and subsequently in hearing, gastrointestinal chloride secretion, and other processes. ML-277 is a potent activator of KCNQ1 channels (EC50 = 260 nM). The EC50 value of this compound at the related channels KCNQ2, KCNQ4, and hERG exceeds 30 μM. ML-277 potentiates both homomultimeric KCNQ1 channels and unsaturated heteromultimeric (KCNQ1/KCNE1) channels in model cardiomyocytes and augments delayed rectifier K+ current in cultured human cardiomyocytes.
