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Adenylyl cyclase/cAMP-PKA-mediated phosphorylation of basal L-type Ca(2+) channels in mouse embryonic ventricular myocytes.

Abstract
In fetal mammalian heart, constitutive adenylyl cyclase/cyclic AMP-dependent protein kinase A (cAMP-PKA)-mediated phosphorylation, independent of β-adrenergic receptor stimulation, could under such circumstances play an important role in sustaining the L-type calcium channel current (I(Ca,L)) and regulating other PKA dependent phosphorylation targets. In this study, we investigated the regulation of L-type Ca(2+) channel (LTCC) in murine embryonic ventricles. The data indicated a higher phosphorylation state of LTCC at early developmental stage (EDS, E9.5-E11.5) than late developmental stage (LDS, E16.5-E18.5). An intrinsic adenylyl cyclase (AC) activity, PKA activity and basal cAMP concentration were obviously higher at EDS than LDS. The cAMP increase in the presence of isobutylmethylxanthine (IBMX, nonselective phosphodiesterase inhibitor) was further augmented at LDS but not at EDS by chelation of intracellular Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-acetoxymethyl ester (BAPTA-AM). Furthermore, I(Ca,L) increased with time after patch rupture in LDS cardiomyocytes dialyzed with pipette solution containing BAPTA whereas not at EDS. Thus we conclude that the high basal level of LTCC phosphorylation is due to the high intrinsic PKA activity and the high intrinsic AC activity at EDS. The latter is possibly owing to the little or no effect of Ca(2+) influx via LTCCs on AC activity, leading to the inability to inhibit AC.
AuthorsXisheng Yan, Shijun Gao, Ming Tang, Jiaoya Xi, Linlin Gao, Minjie Zhu, Hongyan Luo, Xinwu Hu, Yunjie Zheng, Jürgen Hescheler, Huamin Liang
JournalCell calcium (Cell Calcium) Vol. 50 Issue 5 Pg. 433-43 (Nov 2011) ISSN: 1532-1991 [Electronic] Netherlands
PMID21824653 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Ltd. All rights reserved.
Chemical References
  • Calcium Channels, L-Type
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Egtazic Acid
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Adenylyl Cyclases
  • Calcium
  • 1-Methyl-3-isobutylxanthine
Topics
  • 1-Methyl-3-isobutylxanthine (pharmacology)
  • Adenylyl Cyclases (metabolism)
  • Animals
  • Calcium (metabolism)
  • Calcium Channels, L-Type (metabolism)
  • Cyclic AMP (metabolism)
  • Cyclic AMP-Dependent Protein Kinases (metabolism)
  • Egtazic Acid (analogs & derivatives, pharmacology)
  • Electrophysiologic Techniques, Cardiac
  • Embryo, Mammalian
  • Embryonic Development
  • Heart Ventricles (pathology)
  • Membrane Potentials (drug effects)
  • Mice
  • Mice, Inbred Strains
  • Myocytes, Cardiac (drug effects, metabolism, pathology)
  • Phosphorylation

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