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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2011-2-8
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pubmed:abstractText |
Murine ventricular and atrial ATP-sensitive potassium (K(ATP)) channels contain different sulfonylurea receptors (ventricular K(ATP) channels are Kir6.2/SUR2A complexes, while atrial K(ATP) channels are Kir6.2/SUR1 complexes). HMR 1098, the sodium salt of HMR 1883 {1-[[5-[2-(5-chloro-o-anisamido)ethyl]-2-methoxyphenyl]sulfonyl]-3-methylthiourea}, has been considered as a selective sarcolemmal (i.e. SUR2A-dependent) K(ATP) channel inhibitor. However, it is not clear whether HMR 1098 would preferentially inhibit ventricular K(ATP) channels over atrial K(ATP) channels. To test this, we used whole-cell patch clamp techniques on mouse atrial and ventricular myocytes as well as (86)Rb(+) efflux assays and excised inside-out patch clamp techniques on Kir6.2/SUR1 and Kir6.2/SUR2A channels heterologously expressed in COSm6 cells. In mouse atrial myocytes, both spontaneously activated and diazoxide-activated K(ATP) currents were effectively inhibited by 10 ?M HMR 1098. By contrast, in ventricular myocytes, pinacidil-activated K(ATP) currents were inhibited by HMR 1098 at a high concentration (100 ?M) but not at a low concentration (10 ?M). Consistent with this finding, HMR 1098 inhibits (86)Rb(+) effluxes through Kir6.2/SUR1 more effectively than Kir6.2/SUR2A channels in COSm6 cells. In excised inside-out patches, HMR 1098 inhibited Kir6.2/SUR1 channels more effectively, particularly in the presence of MgADP and MgATP (mimicking physiological stimulation). Finally, dose-dependent enhancement of insulin secretion from pancreatic islets and decrease of blood glucose level confirm that HMR 1098 is an inhibitor of Kir6.2/SUR1-composed K(ATP) channels.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Diphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Benzamides,
http://linkedlifedata.com/resource/pubmed/chemical/Blood Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Diazoxide,
http://linkedlifedata.com/resource/pubmed/chemical/HMR 1098,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/KATP Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Pinacidil,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels, Inwardly...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Drug,
http://linkedlifedata.com/resource/pubmed/chemical/sulfonylurea receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1095-8584
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pubmed:author |
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pubmed:copyrightInfo |
Copyright © 2010 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
50
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
552-60
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:21185839-ATP-Binding Cassette Transporters,
pubmed-meshheading:21185839-Adenosine Diphosphate,
pubmed-meshheading:21185839-Adenosine Triphosphate,
pubmed-meshheading:21185839-Animals,
pubmed-meshheading:21185839-Benzamides,
pubmed-meshheading:21185839-Blood Glucose,
pubmed-meshheading:21185839-Diazoxide,
pubmed-meshheading:21185839-Insulin,
pubmed-meshheading:21185839-Islets of Langerhans,
pubmed-meshheading:21185839-KATP Channels,
pubmed-meshheading:21185839-Mice,
pubmed-meshheading:21185839-Mice, Inbred C57BL,
pubmed-meshheading:21185839-Myocytes, Cardiac,
pubmed-meshheading:21185839-Pinacidil,
pubmed-meshheading:21185839-Potassium Channels, Inwardly Rectifying,
pubmed-meshheading:21185839-Receptors, Drug,
pubmed-meshheading:21185839-Sarcolemma,
pubmed-meshheading:21185839-Substrate Specificity
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pubmed:year |
2011
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pubmed:articleTitle |
HMR 1098 is not an SUR isotype specific inhibitor of heterologous or sarcolemmal K ATP channels.
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pubmed:affiliation |
Department of Cell Biology and Physiology, and Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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