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ATP Modulation of ATP-sensitive Potassium Channel ATP Sensitivity Varies with the Type of SUR Subunit

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Affiliated Author(s)
송대규
Alternative Author(s)
Song, Dae Kyu
Journal Title
Journal of Biological Chemistry
ISSN
0021-9258
Issued Date
2001
Abstract
ATP-sensitive potassium (KATP) channels comprise Kir and SUR subunits. Using recombinant KATP channels expressed in Xenopus oocytes, we observed that MgATP (100 μm) block of Kir6.2/SUR2A currents gradually declined with time, whereas inhibition of Kir6.2/SUR1 or Kir6.2ΔC36 currents did not change. The decline in Kir6.2/SUR2A ATP sensitivity was not observed in Mg2+ free solution and was blocked by the phosphatidylinositol (PI) 3-kinase inhibitors LY 294002 (10 μm) and wortmannin (100 μm), and by neomycin (100 μm). These results suggest that a MgATP-dependent synthesis of membrane phospholipids produces a secondary decrease in the ATP sensitivity of Kir6.2/SUR2A. Direct application of the phospholipids PI 4,5-bisphosphate and PI 3,4,5-trisphosphate in the presence of 100 μm MgATP activated all three types of channel, but the response was faster for Kir6.2/SUR2A. Chimeric studies indicate that the different responses of Kir6.2/SUR2A and Kir6.2/SUR1 are mediated by the first six transmembrane domains of SUR. The MgATP-dependent loss of ATP sensitivity of Kir6.2/SUR2A was enhanced by the actin filament disrupter cytochalasin and blocked by phalloidin (which stabilizes the cytoskeleton). Phalloidin did not block the effect of PI 3,4,5-trisphosphate. This suggests that MgATP may cause disruption of the cytoskeleton, leading to enhanced membrane phospholipid levels (or better targeting to the KATPchannel) and thus to decreased channel ATP sensitivity.
Department
Dept. of Physiology (생리학)
Publisher
School of Medicine
Citation
Journal of Biological Chemistry, Vol.276(10) : 7143-7149, 2001
Type
Article
DOI
10.1074/jbc.M009959200
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/33731
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
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