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Glimepiride block of cloned b-cell, cardiac and smooth muscle KATP channels

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Author(s)
Dae-Kyu SongFrances M. Ashcroft
Keimyung Author(s)
Song, Dae Kyu
Department
Dept. of Physiology (생리학)
Journal Title
British Journal of Pharmacology
Issued Date
2001
Volume
133
Issue
1
Abstract
1.We examined the effect of the sulphonylurea glimepiride on three types of recombinant ATP-sensitive potassium (KATP) channels.
2.KATP channels share a common pore-forming subunit, Kir6.2, which associates with different sulphonylurea receptor isoforms (SUR1 in β-cells, SUR2A in heart and SUR2B in smooth muscle).
3.Kir6.2 was coexpressed with SUR1, SUR2A or SUR2B in Xenopus oocytes and macroscopic KATP currents were recorded from giant inside-out membrane patches. Glimepiride was added to the intracellular membrane surface.
4.Glimepiride inhibited Kir6.2/SUR currents by interaction with two sites: a low-affinity site on Kir6.2 (IC50=∼400 μM) and a high-affinity site on SUR (IC50=3.0 nM for SUR1, 5.4 nM for SUR2A and 7.3 nM for SUR2B). The potency of glimepiride at the high-affinity site is close to that observed for glibenclamide (4 nM for SUR1, 27 nM for SUR2A), which has a similar structure.
5.Glimepiride inhibition of Kir6.2/SUR2A and Kir6.2/SUR2B currents, but not Kir6.2/SUR1 currents, reversed rapidly.
6.Our results indicate that glimepiride is a high-affinity sulphonylurea that does not select between the β-cell, cardiac and smooth muscle types of recombinant KATP channel, when measured in inside-out patches. High-affinity inhibition is mediated by interaction of the drug with the sulphonylurea receptor subunit of the channel.
Keywords: ATP-sensitive potassium channel, glimepiride, sulphonylurea, Kir6.2, sulphonylurea receptor
Keimyung Author(s)(Kor)
송대규
Publisher
School of Medicine
Citation
Dae-Kyu Song and Frances M. Ashcroft. (2001). Glimepiride block of cloned b-cell, cardiac and smooth muscle KATP channels. British Journal of Pharmacology, 133(1), 193–199. doi: 10.1038%2Fsj.bjp.0704062
Type
Article
ISSN
0007-1188
DOI
10.1038%2Fsj.bjp.0704062
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35254
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
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