Protein kinase CK2 is coassembled with small conductance Ca ²⁺-activated K⁺ channels and regulates channel gating

Small conductance Ca²⁺-activated K⁺ channels (SK channels) couple the membrane potential to fluctuations in intracellular Ca ²⁺ concentration in many types of cells. SK channels are gated by Ca²⁺ ions via calmodulin that is constitutively bound to the intracellular C terminus of the channels and serves as the Ca²⁺ sensor. Here we show that, in addition, the cytoplasmic N and C termini of the channel protein form a polyprotein complex with the catalytic and regulatory subunits of protein kinase CK2 and protein phosphatase 2A. Within this complex, CK2 phosphorylates calmodulin at threonine 80, reducing by 5-fold the apparent Ca²⁺ sensitivity and accelerating channel deactivation. The results show that native SK channels are polyprotein complexes and demonstrate that the balance between kinase and phosphatase activities within the protein complex shapes the hyperpolarizing response mediated by SK channels.