Figure 5. cAMP may inhibit K_ATP channel function in an Epac-mediated manner.

Nucleotide-binding fold-1 (NBF-1) of the SUR1 subunit of K_ATP channels may recruit Epac to the plasma membrane. Binding of cAMP to Epac may then allow for the activation of plasma membrane-associated Rap GTPase. The activated form of Rap stimulates PLC-ɛ, and the PLC-ɛ-catalysed hydrolysis of PIP₂ results in the closure of K_ATP channels, possibly as a consequence of the increased sensitivity of these channels to ATP. Note that ATP inhibits K_ATP channel function by virtue of its interaction with the Kir6.2 subunit of the channel. In contrast, the activity of K_ATP channels is stimulated by Mg²⁺-ADP, acting at the SUR1 subunit. Abbreviations: W_A and W_B, Walker A and Walker B motifs; TMO, TM1 and TM2, transmembrane clusters; NBF-2, nucleotide-binding fold-2.