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- W2022779856 abstract "Murine ventricular and atrial KATP channels contain different sulfonylurea receptors (ventricular KATP channels are Kir6.2/SUR2A complexes, while atrial KATP channels are Kir6.2/SUR1 complex). HMR 1098, the sodium salt of HMR 1883 {1-[[5-[2-(5-chloro-o-anisamido)ethyl]-2-methoxyphenyl]sulfonyl]-3-methylthiourea}, has been used as a selective sarcolemmal (i.e. SUR2A-dependent) KATP channel inhibitor. However, specificity for ventricular versus atrial channels has not been examined. We used whole-cell patch-clamp techniques on mouse ventricular and atrial myocytes as well as 86Rb+ efflux assays and excised inside-out patch-clamp techniques on Kir6.2/SUR2A and Kir6.2/SUR1 channels heterologously expressed in COSm6 cells. In mouse ventricular myocytes, pinacidil-activated KATP currents were inhibited by HMR 1098 at high (100 ∈μM) but not low (10 ∈μM) concentration. By contrast, in atrial myocytes, both spontaneously activated and diazoxide-activated KATP currents were effectively inhibited by 10 ∈μM HMR 1098. Consistent with this finding, HMR 1098 inhibits 86Rb+ effluxes through Kir6.2/SUR1 more effectively than Kir6.2/SUR2A channels in COSm6 cells. In excised inside-out patches, HMR 1098 effectively inhibited Kir6.2/SUR1 channels as well as Kir6.2/SUR2A channels in the absence of nucleotides, but inhibited Kir6.2/SUR1 channels more effectively than Kir6.2/SUR2A channels in the presence of MgADP and MgATP (mimicking physiological stimulation). Finally, dose-dependent enhancement of insulin secretion from pancreatic islets confirms that HMR 1098 is an effective inhibitor of Kir6.2/SUR1-composed KATP channels, and is not specific for SUR2A-composed channels." @default.
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- W2022779856 date "2010-01-01" @default.
- W2022779856 modified "2023-10-16" @default.
- W2022779856 title "HMR 1098 is not an Sur Isotype Specific Inhibitor of Sarcolemmal or Heterologous KATP Channels" @default.
- W2022779856 doi "https://doi.org/10.1016/j.bpj.2009.12.742" @default.
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