Subtype-selective positive modulation of K 2 channels depends on the HA/HB helices.

Background And Purpose: In the activated state of small-conductance Ca -activated potassium (K 2) channels, calmodulin interacts with the HA/HB helices and the S4-S5 linker. CyPPA potentiates K 2.2a and K 2.

Hydrophobic interactions between the HA helix and S4-S5 linker modulate apparent Ca sensitivity of SK2 channels.

Aim: Small-conductance Ca -activated potassium (SK) channels are activated exclusively by increases in intracellular Ca that binds to calmodulin constitutively associated with the channel. Wild-type SK2 channels are activated by Ca with an EC value of ~0.3 μmol/L.