KATP channels couple cell metabolic status to the membrane excitability by sensing the cytoplasmic ATP/ADP ratio. Present studies examined how conserved motifs (Walker A (WA), signature sequence (L), and Walker B (WB)) within each NBF of SUR2A bind to Syn-1A to affect its actions on cardiac KATP channels. In vitro binding experiments illustrated that Syn-1A binds cardiac SUR2A at WA and L of NBF-1 and WA, L, and WB of NBF-2. Electrophysiology experiments on stably expressing SUR2A/Kir6.2 cell-lines showed that only L and WB of NBF-1 and all three NBF-2 motifs could abrogate the inhibitory effect of Syn-1A on SUR2A/KATP channels. These results lead me to hypothesize that more independent motif in NBF-2 can bind and abrogate Syn-1A’s inhibition than NBF-1 on SUR2A/KATP channels. A corollary postulate is that Syn-1A acts as a scaffold to secure the NBF-1 and -2 in dimer conformation required for SUR2A to modulate Kir6.2 gating.

KATP channels couple cell metabolic status to the membrane excitability by sensing the cytoplasmic ATP/ADP ratio. Present studies examined how conserved motifs (Walker A (WA), signature sequence (L), and Walker B (WB)) within each NBF of SUR2A bind to Syn-1A to affect its actions on cardiac KATP channels. In vitro binding experiments illustrated that Syn-1A binds cardiac SUR2A at WA and L of NBF-1 and WA, L, and WB of NBF-2. Electrophysiology experiments on stably expressing SUR2A/Kir6.2 cell-lines showed that only L and WB of NBF-1 and all three NBF-2 motifs could abrogate the inhibitory effect of Syn-1A on SUR2A/KATP channels. These results lead me to hypothesize that more independent motif in NBF-2 can bind and abrogate Syn-1A’s inhibition than NBF-1 on SUR2A/KATP channels. A corollary postulate is that Syn-1A acts as a scaffold to secure the NBF-1 and -2 in dimer conformation required for SUR2A to modulate Kir6.2 gating.