SK potassium channels share the same basic architecture with Shaker-like voltage-gated potassium channels.  Four subunits associate to form a tetramer.  Each of the subunits has six transmembrane hydrophobic alpha helical domains (S1-S6).  A loop between S5 and S6—called the P-loop—provides the pore-forming region that always faces the center of the channel.  Each of the subunits has six hydrophobic alpha helical domains that insert into the cell membrane.  A loop between the fifth and sixth transmembrane domains forms the potassium ion selectivity filter. SK channels may assemble as homotetrameric channels or as heterotetrameric channels, consisting of more than one SK channel subtype. In addition, SK potassium channels are tightly associated with the protein calmodulin, which accounts for the calcium sensitivity of these channels.  Calmodulin participates as a subunit of the channel itself, bound to the cytoplasmic C-terminus region of the peptide called the calmodulin binding domain (CaMBD).
Additional association of the phosphorylating kinase CK2 and dephosphorylating phosphatase PP2A on the cytoplasmic face of the protein allow for enriched Ca-sensitivity—and thus—kinetics modulation.  CK2 serves to phosphorylate the SKCa-bound CaM at the T80 residue, rather than the channel helices themselves, to reduce calcium sensitivity. This may only be accomplished when the channel pore is closed. PP2A dephosphorylates this residue upon CK2 inhibition. The selectivity filter of all SK channel subtypes—whether SK1, SK2, SK3, or SK4—is highly conserved and reflects the selectivity seen in any potassium channel, a GYGD amino acid residue sequence on the pore-forming loop.  These channels are considered to be voltage-independent, as they possess only two of seven positively charged amino acid residues that are typically seen in a prototypical voltage-gated potassium channel.