International Journal of Clinical and Experimental Medical Sciences

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α1-adrenergic Receptor Attenuates β1-adrenergic Modulation of IKr by Protein Kinase C-dependent Suppression of Adenylyl Cyclase in Ventricular Myocytes

Received: 8 May 2019    Accepted: 10 June 2019    Published: 25 June 2019
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Abstract

The rapid delayed rectifier K+ current (Ikr) is critical for repolarization of the cardiac action potential. Previous studies have shown activated α1-adrenergic receptor (AR) attenuates β1-adrenergic regulation of Ikr while the mechanisms involved are poorly understood. To evalutate how α1-adrenergic receptor affect β1-adrenergic modulation of Ikr, whole-cell patch-clamp recordings were peformed in isolated guinea-pig ventricular myocytes. Application of xamoterol, a selective β1-AR agonist, induced a negative shift in the activation curve and Ikr current reduction by 40.50±6.66% at the test pulse of +40 mV. Forskolin and 8-Br-cAMP also resulted in Ikr reduction by 38.17±1.50% and 24.65±3.37%, respectively. Phenylephrine, a selective α1-AR agonist, prevented the activation shift and Ikr current reduction induced by xamoterol and forskolin, but not by 8-Br-cAMP. The effect of xamoterol or forskolin on Ikr was also prevented by pretreatment with PDBu, a protein kinase C (PKC) activator, while the effect of cAMP on Ikr can not, which was similar to pretreatment with phenylephrine. When cells were pretreated with chelerythrine, a specific PKC inhibitor, phenylephrine failed to prevent Ikr reduction induced by xamoterol. Our data suggests that α1-adrenergic stimulation attenuates β1-adrenergic regulation of Ikr, through PKC-dependent downregulation of adenylyl cyclase/cyclic AMP pathway.

DOI 10.11648/j.ijcems.20190502.11
Published in International Journal of Clinical and Experimental Medical Sciences (Volume 5, Issue 2, March 2019)
Page(s) 26-32
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This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Adrenergic Receptors, Ikr, Cross-talk, Protein Kinase C, Adenylyl Cyclase

References
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  • APA Style

    Sen Wang, Xiaoyan Wang, Jin Qian, Di Xu. (2019). α1-adrenergic Receptor Attenuates β1-adrenergic Modulation of IKr by Protein Kinase C-dependent Suppression of Adenylyl Cyclase in Ventricular Myocytes. International Journal of Clinical and Experimental Medical Sciences, 5(2), 26-32. https://doi.org/10.11648/j.ijcems.20190502.11

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    ACS Style

    Sen Wang; Xiaoyan Wang; Jin Qian; Di Xu. α1-adrenergic Receptor Attenuates β1-adrenergic Modulation of IKr by Protein Kinase C-dependent Suppression of Adenylyl Cyclase in Ventricular Myocytes. Int. J. Clin. Exp. Med. Sci. 2019, 5(2), 26-32. doi: 10.11648/j.ijcems.20190502.11

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    AMA Style

    Sen Wang, Xiaoyan Wang, Jin Qian, Di Xu. α1-adrenergic Receptor Attenuates β1-adrenergic Modulation of IKr by Protein Kinase C-dependent Suppression of Adenylyl Cyclase in Ventricular Myocytes. Int J Clin Exp Med Sci. 2019;5(2):26-32. doi: 10.11648/j.ijcems.20190502.11

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  • @article{10.11648/j.ijcems.20190502.11,
      author = {Sen Wang and Xiaoyan Wang and Jin Qian and Di Xu},
      title = {α1-adrenergic Receptor Attenuates β1-adrenergic Modulation of IKr by Protein Kinase C-dependent Suppression of Adenylyl Cyclase in Ventricular Myocytes},
      journal = {International Journal of Clinical and Experimental Medical Sciences},
      volume = {5},
      number = {2},
      pages = {26-32},
      doi = {10.11648/j.ijcems.20190502.11},
      url = {https://doi.org/10.11648/j.ijcems.20190502.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcems.20190502.11},
      abstract = {The rapid delayed rectifier K+ current (Ikr) is critical for repolarization of the cardiac action potential. Previous studies have shown activated α1-adrenergic receptor (AR) attenuates β1-adrenergic regulation of Ikr while the mechanisms involved are poorly understood. To evalutate how α1-adrenergic receptor affect β1-adrenergic modulation of Ikr, whole-cell patch-clamp recordings were peformed in isolated guinea-pig ventricular myocytes. Application of xamoterol, a selective β1-AR agonist, induced a negative shift in the activation curve and Ikr current reduction by 40.50±6.66% at the test pulse of +40 mV. Forskolin and 8-Br-cAMP also resulted in Ikr reduction by 38.17±1.50% and 24.65±3.37%, respectively. Phenylephrine, a selective α1-AR agonist, prevented the activation shift and Ikr current reduction induced by xamoterol and forskolin, but not by 8-Br-cAMP. The effect of xamoterol or forskolin on Ikr was also prevented by pretreatment with PDBu, a protein kinase C (PKC) activator, while the effect of cAMP on Ikr can not, which was similar to pretreatment with phenylephrine. When cells were pretreated with chelerythrine, a specific PKC inhibitor, phenylephrine failed to prevent Ikr reduction induced by xamoterol. Our data suggests that α1-adrenergic stimulation attenuates β1-adrenergic regulation of Ikr, through PKC-dependent downregulation of adenylyl cyclase/cyclic AMP pathway.},
     year = {2019}
    }
    

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  • TY  - JOUR
    T1  - α1-adrenergic Receptor Attenuates β1-adrenergic Modulation of IKr by Protein Kinase C-dependent Suppression of Adenylyl Cyclase in Ventricular Myocytes
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    JF  - International Journal of Clinical and Experimental Medical Sciences
    JO  - International Journal of Clinical and Experimental Medical Sciences
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    PB  - Science Publishing Group
    SN  - 2469-8032
    UR  - https://doi.org/10.11648/j.ijcems.20190502.11
    AB  - The rapid delayed rectifier K+ current (Ikr) is critical for repolarization of the cardiac action potential. Previous studies have shown activated α1-adrenergic receptor (AR) attenuates β1-adrenergic regulation of Ikr while the mechanisms involved are poorly understood. To evalutate how α1-adrenergic receptor affect β1-adrenergic modulation of Ikr, whole-cell patch-clamp recordings were peformed in isolated guinea-pig ventricular myocytes. Application of xamoterol, a selective β1-AR agonist, induced a negative shift in the activation curve and Ikr current reduction by 40.50±6.66% at the test pulse of +40 mV. Forskolin and 8-Br-cAMP also resulted in Ikr reduction by 38.17±1.50% and 24.65±3.37%, respectively. Phenylephrine, a selective α1-AR agonist, prevented the activation shift and Ikr current reduction induced by xamoterol and forskolin, but not by 8-Br-cAMP. The effect of xamoterol or forskolin on Ikr was also prevented by pretreatment with PDBu, a protein kinase C (PKC) activator, while the effect of cAMP on Ikr can not, which was similar to pretreatment with phenylephrine. When cells were pretreated with chelerythrine, a specific PKC inhibitor, phenylephrine failed to prevent Ikr reduction induced by xamoterol. Our data suggests that α1-adrenergic stimulation attenuates β1-adrenergic regulation of Ikr, through PKC-dependent downregulation of adenylyl cyclase/cyclic AMP pathway.
    VL  - 5
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Author Information
  • Department of Geriatric Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China

  • Department of Geriatric Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China

  • Department of Geriatric Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China

  • Department of Geriatric Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China

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