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    Please use this identifier to cite or link to this item: http://140.128.103.80:8080/handle/310901/28957


    Title: Heterogeneity and function of KATP channels in canine hearts
    Authors: 林玉雯
    Zhang, Hai Xia
    Jonathan, R.Silva
    Lin, Yu-Wen
    W.Verbsky, John
    Lee, Urvi- S
    Evelyn, M.Kanter
    Kathryn, A.Yamada
    Richard, B.Schuessler
    Colin, G.Nichols
    Contributors: Department of Cell Biology and Physiology, Washington University School of Medicine
    Center for the Investigation of Membrane Excitability Diseases, Washington University School of Medicine
    Department of Biomedical Engineering, Washington University School of Medicine
    Department of Medicine, Washington University School of Medicine
    Department of Surgery, Washington University School of Medicine
    Keywords: ATP-sensitive potassium channel
    Sulfonylurea receptor
    Patch-clamp technique
    Action potential duration
    Pinacidil
    Diazoxide
    Metabolic inhibition
    Model simulation
    Canine
    Myocyte
    Date: 2013-10
    Issue Date: 2016-11-24T01:38:41Z (UTC)
    Publisher: Netherlands:Elsevier
    Abstract: Background

    The concept that pore-forming Kir6.2 and regulatory SUR2A subunits form cardiac ATP-sensitive potassium (KATP) channels is challenged by recent reports that SUR1 is predominant in mouse atrial KATP channels.

    Objective

    To assess SUR subunit composition of KATP channels and consequence of KATP activation for action potential duration (APD) in dog hearts.

    Methods

    Patch-clamp techniques were used on isolated dog cardiomyocytes to investigate KATP channel properties. Dynamic current clamp, by injection of a linear K+ conductance to simulate activation of the native current, was used to study the consequences of KATP activation on APD.

    Results

    Metabolic inhibitor (MI)-activated current was not significantly different from pinacidil (SUR2A-specific)-activated current, and both currents were larger than diazoxide (SUR1-specific)-activated current in both the atrium and the ventricle. Mean KATP conductance (activated by MI) did not differ significantly between chambers, although, within the ventricle, both MI-induced and pinacidil-induced currents tended to decrease from the epicardium to the endocardium. Dynamic current-clamp results indicate that myocytes with longer baseline APDs are more susceptible to injected KATP current, a result reproduced in silico by using a canine action potential model (Hund-Rudy) to simulate epicardial and endocardial myocytes.

    Conclusions

    Even a small fraction of KATP activation significantly shortens APD in a manner that depends on existing heterogeneity in KATP current and APD.
    Relation: Heart Rhythm, 10(10), 1576-1583
    Appears in Collections:[生命科學系所] 期刊論文

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