1,724,757 research outputs found

    UMNH:Mamm:4031

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    UMNH:Mamm:4031 Voucher specimen study ski

    Block Card 4031 Hoffman Road

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    This image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Dwelling | 4031 Hoffman Road (Toledo, Ohio) | Bungalow Style | North Toledo Area (Toledo, Ohio

    Chicago, Rock Island & Pacific (RI) 4031

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    A photograph print of Chicago, Rock Island & Pacific (CRIP, RI, or ROCK) 4031, 4-8-2, on a passenger train, Topeka, KS

    Inhibition of the hERG Potassium Channel by a Methanesulphonate-Free E-4031 Analogue

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    hERG (human Ether-à-go-go Related Gene)-encoded potassium channels underlie the cardiac rapid delayed rectifier (IKr) potassium current, which is a major target for antiarrhythmic agents and diverse non-cardiac drugs linked to the drug-induced form of long QT syndrome. E-4031 is a high potency hERG channel inhibitor from the methanesulphonanilide drug family. This study utilized a methanesulphonate-lacking E-4031 analogue, “E-4031-17”, to evaluate the role of the methanesulphonamide group in E-4031 inhibition of hERG. Whole-cell patch-clamp measurements of the hERG current (IhERG) were made at physiological temperature from HEK 293 cells expressing wild-type (WT) and mutant hERG constructs. For E-4031, WT IhERG was inhibited by a half-maximal inhibitory concentration (IC50) of 15.8 nM, whilst the comparable value for E-4031-17 was 40.3 nM. Both compounds exhibited voltage- and time-dependent inhibition, but they differed in their response to successive applications of a long (10 s) depolarisation protocol, consistent with greater dissociation of E-4031-17 than the parent compound between applied commands. Voltage-dependent inactivation was left-ward voltage shifted for E-4031 but not for E-4031-17; however, inhibition by both compounds was strongly reduced by attenuated-inactivation mutations. Mutations of S6 and S5 aromatic residues (F656V, Y652A, F557L) greatly attenuated actions of both drugs. The S624A mutation also reduced IhERG inhibition by both molecules. Overall, these results demonstrate that the lack of a methanesulphonate in E-4031-17 is not an impediment to high potency inhibition of IhERG

    Block Card 4031 Peak Avenue

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    This image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Dwelling | 4031 Peak Avenue (Toledo, Ohio) | Willys Park Area (Toledo, Ohio) | West Toledo Area (Toledo, Ohio) | Gable front houses | Folk House Styl

    Block Card 4031 Walker Avenue

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    This image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Dwelling | 4031 Walker Avenue (Toledo, Ohio) | Willys Park Area (Toledo, Ohio) | West Toledo Area (Toledo, Ohio) | Modern Colonial Styl

    Block Card 4031 Wetzler Road

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    This image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Dwelling (Toledo, Ohio) | Folk House Style | sleeping porch | porte cochere | Craftsman Style | Homeville Subdivision (Toledo, Ohio) | Willys Park area (Toledo, Ohio) | West Toledo (Toledo, Ohio) | 4031 Wetzler Road (Toledo, Ohio

    Block Card 4031 Gilhouse Road

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    This image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Split-Level Style | 4031 Gilhouse Road (Toledo, Ohio) | Dwelling | Grandview Woods Addition (Toledo, Ohio) | Trilby Area (Toledo, Ohio)

    Different electrophysiologic effects of E-4031 in two distinct populations of beating clusters.

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    <p>E-4031-induced I<sub>Kr</sub> block leads to EADs in cells from some beating clusters, but results in depolarization of cells in the majority of BC. <b>A and B</b>: Shown are action potential (AP), V<sub>max</sub> and contraction (Edge Motion) recordings from a 69 day-old <b>(A)</b> and a 102 day-old <b>(B)</b> beating clusters under control conditions and following the addition of 5 µM E-4031. In <b>A</b>, E-4031 induced EADs within 5 min. In <b>B</b>, E-4031 led to depolarization within 3 to 4 min.</p
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