Apamin-Sensitive Calcium-Activated Potassium Currents in Rabbit Ventricles with Chronic Myocardial Infarction

Authors

  • YOUNG SOO LEE M.D., Ph.D.,

    1. Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indianapolis, Indiana, USA
    2. Division of Cardiology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea
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  • PO-CHENG CHANG M.D.,

    1. Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indianapolis, Indiana, USA
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  • CHIA-HSIANG HSUEH Ph.D.,

    1. Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indianapolis, Indiana, USA
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  • MITSUNORI MARUYAMA M.D., Ph.D.,

    1. Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indianapolis, Indiana, USA
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  • HYUNG WOOK PARK M.D., Ph.D.,

    1. Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indianapolis, Indiana, USA
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  • KYOUNG-SUK RHEE M.D., Ph.D.,

    1. Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indianapolis, Indiana, USA
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  • YU-CHENG HSIEH M.D., Ph.D.,

    1. Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indianapolis, Indiana, USA
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  • CHANGYU SHEN Ph.D.,

    1. Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana, USA
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  • JAMES N. WEISS M.D.,

    1. Cardiovascular Research Laboratory, Departments of Medicine (Cardiology) and Physiology, David Geffen School of Medicine, University of California, Los Angeles, California, USA
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  • ZHENHUI CHEN Ph.D.,

    1. Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indianapolis, Indiana, USA
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  • SHIEN-FONG LIN Ph.D.,

    1. Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indianapolis, Indiana, USA
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  • PENG-SHENG CHEN M.D.

    Corresponding author
    • Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indianapolis, Indiana, USA
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  • This study was supported in part by National Institutes of Health grants P01 HL78931, R01 HL78932, R01 71140, and R21 HL106554; and by the Laubisch and Kawata Endowments of the University of California Los Angeles (Dr. J. Weiss), a Medtronic-Zipes Endowment of Indiana University (Dr. P. Chen) and the Indiana University Health-Indiana University School of Medicine Strategic Research Initiative.

  • Medtronic Inc., St. Jude Inc., Cryocath Inc., and Cyberonics Inc. donated research equipment to Dr. Chen's laboratory. Dr. Chen is a consultant to Cyberonics Inc. Other authors: No disclosures.

Address for correspondence: Peng-Sheng Chen, M.D., 1801 N. Capitol Ave., E475, Indianapolis, IN 46202, USA. Fax: 317-962-0588, E-mail: chenpp@iu.edu

SK Currents in Chronic MI

Introduction

The apamin-sensitive small-conductance calcium-activated potassium current (IKAS) is increased in heart failure. It is unknown if myocardial infarction (MI) is also associated with an increase of IKAS.

Methods and Results

We performed Langendorff perfusion and optical mapping in 6 normal hearts and 10 hearts with chronic (5 weeks) MI. An additional 6 normal and 10 MI hearts were used for patch clamp studies. The infarct size was 25% (95% confidence interval, 20–31) and the left ventricular ejection fraction was 50 (46–54). The rabbits did not have symptoms of heart failure. The action potential duration measured to 80% repolarization (APD80) in the peri-infarct zone (PZ) was 150 (142–159) milliseconds, significantly (P = 0.01) shorter than that in the normal ventricles (167 [158–177] milliseconds. The intracellular Ca transient duration was also shorter in the PZ (148 [139–157] milliseconds) than that in normal ventricles (168 [157–180] milliseconds; P = 0.017). Apamin prolonged the APD80 in PZ by 9.8 (5.5–14.1)%, which is greater than that in normal ventricles (2.8 [1.3–4.3]%, P = 0.006). Significant shortening of APD80 was observed at the cessation of rapid pacing in MI but not in normal ventricles. Apamin prevented postpacing APD80 shortening. Patch clamp studies showed that IKAS was significantly higher in the PZ cells (2.51 [1.55–3.47] pA/pF, N = 17) than in the normal cells (1.08 [0.36–1.80] pA/pF, N = 15, P = 0.019).

Conclusion

We conclude that IKAS is increased in MI ventricles and contributes significantly to ventricular repolarization especially during tachycardia.

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