NS309 is a nonselective activator of small- and intermediate-conductance Ca2+-activated K+ (SK/KCa2 and IK/KCa3.1) channels (EC50s range from 0.12-1.2 μM for SK channels and 10-90 nM for IK channels). It can also activate voltage-gated Kv11.1 channels (hERG; IC50 = 1 μM), but does not, however, affect large conductance (BK/KCa1.1) channels. NS309 can modulate neuronal firing patterns by enhancing SK-mediated hyperpolarizing effects. It is 730-fold (SK channels) and 7,400-fold (IK channels) more potent than 1-EBIO and often used in conjunction with CyPPA to distinguish between SK1 and SK3 subtypes.
