Diadenosine tetraphosphate (Ap4A) has been recently discovered in the pancreatic γ cells where targets ATP-sensitive K+ (KATP) channels, depolarizes the cell membrane and induces insulin secretion. However, whether Ap4A inhibit pancreatic KATP channels by targeting protein channel complex itself was unknown. Therefore, we coexpressed pancreatic KATP channel subunits, Kir6.2 and SUR1, in COS-7 cells and examined the effect of Ap4A on the single channel behavior using the inside-out configuration of the patch-clamp technique. Ap4A inhibited channel opening in a concentration-dependent manner. Analysis of single channels demonstrated that Ap4A did not change intraburst kinetic behavior of KATP channels, but rather decreased burst duration and increased between-burst duration. It is concluded that Ap4A antagonizes KATP channel opening by targeting channel subunits themselves and by keeping channels longer in closed interburst states.
Research Article| February 01 2001
Diadenosine Tetraphosphate-Gating of Recombinant Pancreatic ATP-Sensitive K+ Channels
Biosci Rep (2001) 21 (1): 93–99.
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Sofija Jovanovic, Aleksandar Jovanovic; Diadenosine Tetraphosphate-Gating of Recombinant Pancreatic ATP-Sensitive K+ Channels. Biosci Rep 1 February 2001; 21 (1): 93–99. doi: https://doi.org/10.1023/A:1010442303427
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