SKA-121

SKA-121 is a positive-gating modulator of intermediate-conductance calcium-activated potassium channels (IKCa1/KCa3.1) with an EC50 value of 109 nM using whole-cell patch-clamp electrophysiology with calcium in the internal solution.{41411} It is selective for KCa3.1 over KCa2.1, KCa2.2 and KCa2.3 (EC50s = 8,700, 6,800, and 4,400 nM, respectively).{41410} It is also selective over KCa1.1 as well as voltage-gated potassium and sodium channels. SKA-121 (1 µM) potentiates calcium-evoked KCa currents by approximately 7-fold using whole-cell patch-clamp electrophysiology, an effect that can be blocked by the KCa3.1 inhibitor TRAM-34 (Item No. 23385).{41411} It also potentiates calcium-evoked and basal KCa currents. In large porcine coronary arteries ex vivo, SKA-121 potentiates bradykinin-induced endothelium-dependent relaxation (EC50 = 7.9 nM). It also lowers mean arterial blood pressure (MAP) by approximately 20 and 25 mm Hg in normo- and hypertensive mice when used at a dose of 100 mg/kg but has no effect on MAP in KCa3.1 knockout mice.{41410}