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Beta-adrenergic stimulation reverses the I Kr–I Ks dominant pattern during cardiac action potential

  • Ion channels, receptors and transporters
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Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

β-Adrenergic stimulation differentially modulates different K+ channels and thus fine-tunes cardiac action potential (AP) repolarization. However, it remains unclear how the proportion of I Ks, I Kr, and I K1 currents in the same cell would be altered by β-adrenergic stimulation, which would change the relative contribution of individual K+ current to the total repolarization reserve. In this study, we used an innovative AP-clamp sequential dissection technique to directly record the dynamic I Ks, I Kr, and I K1 currents during the AP in guinea pig ventricular myocytes under physiologically relevant conditions. Our data provide quantitative measures of the magnitude and time course of I Ks, I Kr, and I K1 currents in the same cell under its own steady-state AP, in a physiological milieu, and with preserved Ca2+ homeostasis. We found that isoproterenol treatment significantly enhanced I Ks, moderately increased I K1, but slightly decreased I Kr in a dose-dependent manner. The dominance pattern of the K+ currents was I Kr > I K1 > I Ks at the control condition, but reversed to I Kr < I K1 < I Ks following β-adrenergic stimulation. We systematically determined the changes in the relative contribution of I Ks, I Kr, and I K1 to cardiac repolarization during AP at different adrenergic states. In conclusion, the β-adrenergic stimulation fine-tunes the cardiac AP morphology by shifting the power of different K+ currents in a dose-dependent manner. This knowledge is important for designing antiarrhythmic drug strategies to treat hearts exposed to various sympathetic tones.

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Acknowledgments

We are grateful to Dr. Donald M. Bers for doing an internal review and editing of the manuscript. This work was supported by the National Institute of Health R01 grant (HL90880) to LTI, YC, and TB; the National Institute of Health R03 grant (AG031944) to YC; American Heart Association National Center Scientist Development Award (0335250 N) to YC; European Society of Cardiology Visiting Scientist Award to BH; the Hungarian Research Fund OTKA (K101196) to TB; and the startup funds from the University of California to LTI and YC.

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Authors and Affiliations

  1. Department of Pharmacology, University of California, 2221 Tupper Hall, 451 Health Science Drive, Davis, CA, 95616, USA

    Tamas Banyasz, Zhong Jian, Balazs Horvath, Shaden Khabbaz, Leighton T. Izu & Ye Chen-Izu

  2. Department of Physiology, University of Debrecen, MHSC, Debrecen, Hungary

    Tamas Banyasz

  3. Department of Biomedical Engineering, University of California, Davis, CA, USA

    Ye Chen-Izu

  4. Department of Internal Medicine, Division of Cardiology, University of California, Davis, CA, USA

    Ye Chen-Izu

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  1. Tamas Banyasz
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  2. Zhong Jian
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  5. Leighton T. Izu
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Correspondence to Ye Chen-Izu.

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Tamas Banyasz and Zhong Jian are the first authors with equal contribution.

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Banyasz, T., Jian, Z., Horvath, B. et al. Beta-adrenergic stimulation reverses the I Kr–I Ks dominant pattern during cardiac action potential. Pflugers Arch - Eur J Physiol 466, 2067–2076 (2014). https://doi.org/10.1007/s00424-014-1465-7

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  • DOI: https://doi.org/10.1007/s00424-014-1465-7

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