Abstract
BK type Ca2+-activated K+ channels activate in response to both the membrane voltage and intracellular Ca2+. The later binds to two classes of binding sites located in the cytosolic domain, known as the gating ring. However, how Ca2+ binding opens the activation gate in the membrane spanning the pore-gate domain is not clear. Using molecular docking to screen a compound library we identified BC5 that binds at the interface between the voltage sensor domain (VSD) and the gating ring, which was validated by mutagenesis studies.
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