ABCMdb

PMID: 9618560

Gribble FM, Tucker SJ, Haug T, Ashcroft FM
MgATP activates the beta cell KATP channel by interaction with its SUR1 subunit.
Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):7185-90., [PubMed]

Sentences

No. Mutations Sentence Comment

7 ABCC8 p.Lys719Ala ABCC8 p.Lys1384Met ABCC8 p.Asp853Asn ABCC8 p.Asp1505Asn Both of these effects were abolished when mutations were made in the NBDs of SUR1 that are predicted to abolish MgATP binding and/or hydrolysis (D853N, D1505N, K719A, or K1384M). Login to comment 106 ABCC8 p.Asp853Asn ABCC8 p.Asp1505Asn We therefore explored the effects of mutation of the WB aspartate to asparagine in either the first (D853N) or the second (D1505N) NBD on the sensitivity of the channel to inhibition by ATP. Login to comment 107 ABCC8 p.Asp853Asn ABCC8 p.Asp1505Asn Giant patches excised from oocytes coinjected with mRNAs encoding Kir6.2 and either D853N-SUR1 or D1505N-SUR1 developed large Kϩ currents, which were of comparable amplitude to those observed for wild-type channels, after patch excision. Login to comment 108 ABCC8 p.Asp853Asn ABCC8 p.Asp1505Asn The mean macroscopic conductance was 95 Ϯ 24 nS (n ϭ 5) for D853N-SUR1 channels, 48 Ϯ 16 nS (n ϭ 8) for D1505N-SUR1 channels, and 49 Ϯ 6 nS (n ϭ 18) for wild-type channels. Login to comment 110 ABCC8 p.Asp853Asn ABCC8 p.Asp1505Asn Fig. 2 compares the relationship between ATP concentration and channel inhibition for wild-type, D853N-SUR1, and D1505N-SUR1 currents. Login to comment 112 ABCC8 p.Asp853Asn ABCC8 p.Asp1505Asn The Ki for ATP inhibition of D853N-SUR1 currents was 13.4 Ϯ 0.2 ␮M (n ϭ 4), and that of D1505N-SUR1 was 16.0 Ϯ 2.6 ␮M (n ϭ 5), compared with 28 ␮M for wild-type currents (P ϭ 0.05 by ANOVA). Login to comment 134 ABCC8 p.Asp853Asn ABCC8 p.Asp1505Asn Mean ATP dose-response relationships for Kir6.2͞SUR1 (f, n ϭ 15), Kir6.2͞SUR1-D853N (⅜, n ϭ 4) or Kir6.2͞SUR1-D1505N (F, n ϭ 5) currents, measured in the presence of Mg2ϩ. Login to comment