Volume 5, Issue 2, March 2019, Page: 26-32
α1-adrenergic Receptor Attenuates β1-adrenergic Modulation of IKr by Protein Kinase C-dependent Suppression of Adenylyl Cyclase in Ventricular Myocytes
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
Received: May 8, 2019;       Accepted: Jun. 10, 2019;       Published: Jun. 25, 2019
DOI: 10.11648/j.ijcems.20190502.11      View  171      Downloads  19
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.
Keywords
Adrenergic Receptors, Ikr, Cross-talk, Protein Kinase C, Adenylyl Cyclase
To cite this article
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, International Journal of Clinical and Experimental Medical Sciences. Vol. 5, No. 2, 2019, pp. 26-32. doi: 10.11648/j.ijcems.20190502.11
Copyright
Copyright © 2019 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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