NS-11021

NS-11021 is a synthetic, potent and selective activator of K_Ca1.1 - the large conductance Ca²⁺-activated K⁺-channel with an EC₅₀ value of 0.4 µM K_Ca1.1. NS-11021 affects K_Ca1.1 in both their open and closed states. Application of NS-11021 (3 µM) increased Kca1.1 currents by 171±31% for channels that shift between open and closed state and by 187±27% for channels kept in closed conformation in Xenopus oocytes heterologously expressing hK_Ca1.1. NS-11021 also produces a negative shift in the threshold for current activation and increases the peak tail current amplitude for K_Ca1.1 channels. NS-11021 also activates the KCNQ4 (K_V7.4) channel at high concentrations but has a minor or no effect on other potassium and calcium channels. NS-11021 is effective when exposed to either side of the cell’s membrane and most likely exerts its effect through direct binding to the K_Ca1.1 α-subunit¹.