Yan, Xisheng, Gao, Shijun, Tang, Ming, Xi, Jiaoya, Gao, Linlin, Zhu, Minjie, Luo, Hongyan, Hu, Xinwu, Zheng, Yunjie, Hescheler, Juergen and Liang, Huamin (2011). Adenylyl cyclase/cAMP-PKA-mediated phosphorylation of basal L-type Ca2+ channels in mouse embryonic ventricular myocytes. Cell Calcium, 50 (5). S. 433 - 444. EDINBURGH: CHURCHILL LIVINGSTONE. ISSN 0143-4160

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Abstract

In fetal mammalian heart, constitutive adenylyl cyclase/cyclic AMP-dependent protein kinase A (cAMP-PKA)-mediated phosphorylation, independent of P-adrenergic receptor stimulation, could under such circumstances play an important role in sustaining the L-type calcium channel current (I-Ca,I-L) and regulating other PKA dependent phosphorylation targets. In this study, we investigated the regulation of L-type Ca2+ 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 Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-acetoxymethyl ester (BAPTA-AM). Furthermore, I-Ca,I-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 PICA activity and the high intrinsic AC activity at EDS. The latter is possibly owing to the little or no effect of Ca2+ influx via LTCCs on AC activity, leading to the inability to inhibit AC. (C) 2011 Elsevier Ltd. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Yan, XishengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gao, ShijunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tang, MingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xi, JiaoyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gao, LinlinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhu, MinjieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luo, HongyanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hu, XinwuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zheng, YunjieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hescheler, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liang, HuaminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-486040
DOI: 10.1016/j.ceca.2011.07.004
Journal or Publication Title: Cell Calcium
Volume: 50
Number: 5
Page Range: S. 433 - 444
Date: 2011
Publisher: CHURCHILL LIVINGSTONE
Place of Publication: EDINBURGH
ISSN: 0143-4160
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DEPENDENT PROTEIN-KINASE; BETA-ADRENERGIC STIMULATION; CALCIUM-CHANNELS; CARDIAC MYOCYTES; PHOSPHATASE 2A; FUNCTIONAL EXPRESSION; CA(V)1.2 PHOSPHORYLATION; OPEN PROBABILITY; PACEMAKER CELLS; ALPHA-1 SUBUNITMultiple languages
Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/48604

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