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Open AccessArticle

Regulation of IKs Potassium Current by Isoproterenol in Adult Cardiomyocytes Requires Type 9 Adenylyl Cyclase

1
Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA
2
Department of Pharmacology, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2019, 8(9), 981; https://doi.org/10.3390/cells8090981
Received: 3 July 2019 / Revised: 20 August 2019 / Accepted: 23 August 2019 / Published: 27 August 2019
(This article belongs to the Special Issue New Advances in Cyclic AMP Signalling)
The subunits KCNQ1 and KCNE1 generate the slowly activating, delayed rectifier potassium current, IKs, that responds to sympathetic stimulation and is critical for human cardiac repolarization. The A-kinase anchoring protein Yotiao facilitates macromolecular complex formation between IKs and protein kinase A (PKA) to regulate phosphorylation of KCNQ1 and IKs currents following beta-adrenergic stimulation. We have previously shown that adenylyl cyclase Type 9 (AC9) is associated with a KCNQ1-Yotiao-PKA complex and facilitates isoproterenol-stimulated phosphorylation of KCNQ1 in an immortalized cell line. However, requirement for AC9 in sympathetic control of IKs in the heart was unknown. Using a transgenic mouse strain expressing the KCNQ1-KCNE1 subunits of IKs, we show that AC9 is the only adenylyl cyclase (AC) isoform associated with the KCNQ1-KCNE1-Yotiao complex in the heart. Deletion of AC9 resulted in the loss of isoproterenol-stimulated KCNQ1 phosphorylation in vivo, even though AC9 represents less than 3% of total cardiac AC activity. Importantly, a significant reduction of isoproterenol-stimulated IKs currents was also observed in adult cardiomyocytes from IKs-expressing AC9KO mice. AC9 and Yotiao co-localize with N-cadherin, a marker of intercalated disks and cell–cell junctions, in neonatal and adult cardiomyocytes, respectively. In conclusion, AC9 is necessary for sympathetic regulation of PKA phosphorylation of KCNQ1 in vivo and for functional regulation of IKs in adult cardiomyocytes. View Full-Text
Keywords: adenylyl cyclase; AC9; A-kinase anchoring protein; AKAP; cyclic AMP; cardiomyocyte; Yotiao; KCNQ1; protein kinase A; potassium channels adenylyl cyclase; AC9; A-kinase anchoring protein; AKAP; cyclic AMP; cardiomyocyte; Yotiao; KCNQ1; protein kinase A; potassium channels
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MDPI and ACS Style

Li, Y.; Hof, T.; Baldwin, T.A.; Chen, L.; Kass, R.S.; Dessauer, C.W. Regulation of IKs Potassium Current by Isoproterenol in Adult Cardiomyocytes Requires Type 9 Adenylyl Cyclase. Cells 2019, 8, 981. https://doi.org/10.3390/cells8090981

AMA Style

Li Y, Hof T, Baldwin TA, Chen L, Kass RS, Dessauer CW. Regulation of IKs Potassium Current by Isoproterenol in Adult Cardiomyocytes Requires Type 9 Adenylyl Cyclase. Cells. 2019; 8(9):981. https://doi.org/10.3390/cells8090981

Chicago/Turabian Style

Li, Yong; Hof, Thomas; Baldwin, Tanya A.; Chen, Lei; Kass, Robert S.; Dessauer, Carmen W. 2019. "Regulation of IKs Potassium Current by Isoproterenol in Adult Cardiomyocytes Requires Type 9 Adenylyl Cyclase" Cells 8, no. 9: 981. https://doi.org/10.3390/cells8090981

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