Investigating the Impact of Electrostatic Interactions on Calmodulin Binding and Ca-Dependent Activation of the Calcium-Gated Potassium SK4 Channel.

Ca binding to the ubiquitous Ca sensing protein calmodulin (CaM) activates the intermediate conductance Ca-activated SK4 channel. Potential hydrophilic pockets for CaM binding have been identified at the intracellular HA and HB helices in the C-terminal of SK4 from the three published cryo-EM structures of SK4. Single charge reversal substitutions at either site, significantly weakened the pull-down of SK4 by CaM wild-type (CaM), and decreased the TRAM-34 sensitive outward K current densities in native HEK293T cells when compared with SK4 WT measured under the same conditions.