Role of the C‐terminus of SUR in the differential regulation of β‐cell and cardiac KATP channels by MgADP and metabolism

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp13230-list-0001">β‐Cell KATP channels are partially open in the absence of metabolic substrates, whereas cardiac KATP channels are closed.Using cloned channels heterologously expressed in Xenopus oocytes we measured the effect of MgADP on the MgATP concentration–inhibition curve immediately after patch excision.MgADP caused a far more striking reduction in ATP inhibition of Kir6.2/SUR1 channels than Kir6.2/SUR2A channels; this effect declined rapidly after patch excision.Exchanging the final 42 amino acids of SUR was sufficient to switch the Mg‐nucleotide regulation of Kir6.2/SUR1 and Kir6.2/SUR2A channels, and partially switch their sensitivity to metabolic inhibition.Deletion of the C‐terminal 42 residues of SUR abolished MgADP activation of both Kir6.2/SUR1 and Kir6.2/SUR2A channels.We conclude that the different metabolic sensitivity of Kir6.2/SUR1 and Kir6.2/SUR2A channels is at least partially due to their different regulation by Mg‐nucleotides, which is determined by the final 42 amino acids.