α<sub>1</sub>-adrenergic Receptor Attenuates β<sub>1</sub>-adrenergic Modulation of IKr by Protein Kinase C-dependent Suppression of Adenylyl Cyclase in Ventricular Myocytes

Sen Wang; Xiaoyan Wang; Jin Qian; Di Xu

doi:doi:10.11648/j.ijcems.20190502.11

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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

Sen Wang, Xiaoyan Wang, Jin Qian, Di Xu

Published in International Journal of Clinical and Experimental Medical Sciences (Volume 5, Issue 2)

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

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Abstract

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

Published in	International Journal of Clinical and Experimental Medical Sciences (Volume 5, Issue 2)
DOI	10.11648/j.ijcems.20190502.11
Page(s)	26-32
Creative Commons	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), 2019. Published by Science Publishing Group

Keywords

Adrenergic Receptors, I_kr, 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
AU  - Sen Wang
AU  - Xiaoyan Wang
AU  - Jin Qian
AU  - Di Xu
Y1  - 2019/06/25
PY  - 2019
N1  - https://doi.org/10.11648/j.ijcems.20190502.11
DO  - 10.11648/j.ijcems.20190502.11
T2  - International Journal of Clinical and Experimental Medical Sciences
JF  - International Journal of Clinical and Experimental Medical Sciences
JO  - International Journal of Clinical and Experimental Medical Sciences
SP  - 26
EP  - 32
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
IS  - 2
ER  -

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Author Information

Sen Wang

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

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

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

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

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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

Copy | Download

@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}
}

Copy | Download

TY  - JOUR
T1  - α1-adrenergic Receptor Attenuates β1-adrenergic Modulation of IKr by Protein Kinase C-dependent Suppression of Adenylyl Cyclase in Ventricular Myocytes
AU  - Sen Wang
AU  - Xiaoyan Wang
AU  - Jin Qian
AU  - Di Xu
Y1  - 2019/06/25
PY  - 2019
N1  - https://doi.org/10.11648/j.ijcems.20190502.11
DO  - 10.11648/j.ijcems.20190502.11
T2  - International Journal of Clinical and Experimental Medical Sciences
JF  - International Journal of Clinical and Experimental Medical Sciences
JO  - International Journal of Clinical and Experimental Medical Sciences
SP  - 26
EP  - 32
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
IS  - 2
ER  -

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