ABCMdb

PMID: 12198249

Light PE, Manning Fox JE, Riedel MJ, Wheeler MB
Glucagon-like peptide-1 inhibits pancreatic ATP-sensitive potassium channels via a protein kinase A- and ADP-dependent mechanism.
Mol Endocrinol. 2002 Sep;16(9):2135-44., [PubMed]

Sentences

No. Mutations Sentence Comment

8 ABCC8 p.Ser1448Ala The point mutation S1448A in the ADP-sensing region of SUR1 removed the modulatory effects of cPKA. Login to comment 87 ABCC8 p.Ser1448Ala We therefore generated a S1448A substitution mutant in the hamster SUR1 sequence and coexpressed this mutant with Kir6.2. Login to comment 88 ABCC8 p.Ser1448Ala Inside-out patch experiments revealed that the S1448A mutant was functionally expressed and possessed similar ATP and ADP-sensing properties when compared with WT SUR1/Kir6.2 channels (Fig. 5D). Login to comment 89 ABCC8 p.Ser1448Ala Under the identical conditions that produced a cPKA- induced significant reduction in WT KATP channel current (0.2 mM ATP and 0.2 mM ADP), SUR1(S1448A)/ Kir6.2 current was not significantly changed in the presence of 20 nM cPKA [95.40 Ϯ 2.8%, n ϭ 8 patches (P Ͼ 0.05), Fig. 5, A and C]. Login to comment 99 ABCC8 p.Ser1448Ala cPKA, the SUR1(S1448A)/Kir6.2 current was also unaffected by application of cPKA (95.31 Ϯ 5.94, n ϭ 13 patches, Fig. 5B). Login to comment 146 ABCC8 p.Ser1448Ala ABCC8 p.Ser1448Ala The Effects of Purified PKA on Recombinant WT or KATP Channels Expressing the SUR1 Substitution Mutant, SUR1(S1448A) A and B, Representative recordings of Kir6.2/SUR1(S1448A) currents from excised inside-out membrane patches from tsA201 cells in response to application of 20 nM cPKA in the presence of either 0.2 mM ADP (A) or 0.5 mM ADP (B). Login to comment 148 ABCC8 p.Ser1448Ala C, Grouped data from WT (Kir6.2/ SUR1) or mutated (S1448A) KATP channels in response to application of cPKA, either in the presence or absence of ADP (0.2 mM) and ATP (0.2 mM) ATP continuously present. Login to comment 150 ABCC8 p.Ser1448Ala D, Grouped data, from inside-out patch experiments with WT and S1448A mutant KATP channels, showing a similar response to ATP alone (0.2 mM) and a release of this ATP-induced inhibition by ADP (0.2 mM). Login to comment 151 ABCC8 p.Ser1448Ala There were no statistical differences in nucleotide sensitivities between WT and S1448A KATP channels. Login to comment 196 ABCC8 p.Ser1448Ala Molecular Biology The S1448A point mutation was introduced into the hamster SUR1 clone, using the Unique Site Elimination (U.S.E.) Mutagenesis Kit as per the manufacturer`s instructions (Amersham Pharmacia Biotech, Piscataway, NJ) and confirmed by sequence analysis. Login to comment