PMID- 10206966
OWN - NLM
STAT- MEDLINE
DCOM- 19990520
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 17
DP  - 1999 Apr 23
TI  - Two regions of sulfonylurea receptor specify the spontaneous bursting and ATP
      inhibition of KATP channel isoforms.
PG  - 11587-92
AB  - KATP channels are heteromultimers of KIR6.2 and a sulfonylurea receptor, SUR, an 
      ATP binding cassette (ABC) protein with several isoforms. KIR6.2 forms a channel 
      pore whose spontaneous activity and ATP sensitivity are modulated by the receptor
      via an unknown interaction(s). Side by side comparison of single-channel kinetics
      and steady-state ATP inhibition of human beta-cell, SUR1/KIR6.2, versus cardiac, 
      SUR2A/KIR6.2 channels demonstrate that the latter have a greater mean burst
      duration and open probability in the absence of nucleotides and approximately
      4-fold higher IC50(ATP). We have used matched chimeras of SUR1 and SUR2A to show 
      that the kinetics, which determine the maximal open probability (Pomax), and the 
      ATP sensitivity are functionally separable and to identify the two segments of
      SUR responsible for these isoform differences. A region within the first five
      transmembrane domains specifies the interburst kinetics, whereas a C-terminal
      segment determines the sensitivity to inhibitory ATP. The separable effects of
      SUR on ATP inhibition and channel kinetics implies that the cytoplasmic C
      terminus of SUR either directly modulates the affinity of a weak ATP binding site
      on the inward rectifier or affects linkage between the binding site and the gate.
      This is the first identification of parts of an ABC protein that interact with an
      ion channel subunit to modulate the spontaneous activity and ATP sensitivity of
      the heteromeric channel.
FAU - Babenko, A P
AU  - Babenko AP
AD  - Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030,
      USA. ababenko@bcm.tmc.edu
FAU - Gonzalez, G
AU  - Gonzalez G
FAU - Bryan, J
AU  - Bryan J
LA  - eng
GR  - DK44311/DK/NIDDK NIH HHS/United States
GR  - DK52771/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (ABCC8 protein, human)
RN  - 0 (ABCC9 protein, human)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (KATP Channels)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Inwardly Rectifying)
RN  - 0 (Protein Isoforms)
RN  - 0 (Receptors, Drug)
RN  - 0 (Sulfonylurea Receptors)
RN  - 0 (uK-ATP-1 potassium channel)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - *ATP-Binding Cassette Transporters
MH  - Adenosine Triphosphate/*pharmacology
MH  - Animals
MH  - COS Cells
MH  - Humans
MH  - Ion Channel Gating
MH  - KATP Channels
MH  - Kinetics
MH  - *Potassium Channel Blockers
MH  - Potassium Channels/chemistry/*metabolism
MH  - *Potassium Channels, Inwardly Rectifying
MH  - Protein Isoforms/*antagonists & inhibitors
MH  - Receptors, Drug/chemistry/*metabolism
MH  - Sulfonylurea Receptors
EDAT- 1999/04/17 00:00
MHDA- 1999/04/17 00:01
CRDT- 1999/04/17 00:00
PHST- 1999/04/17 00:00 [pubmed]
PHST- 1999/04/17 00:01 [medline]
PHST- 1999/04/17 00:00 [entrez]
AID - 10.1074/jbc.274.17.11587 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Apr 23;274(17):11587-92. doi: 10.1074/jbc.274.17.11587.