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

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.

Yan X ，Gao S ，Tang M ，Xi J ，Gao L ，Zhu M ，Luo H ，Hu X ，Zheng Y ，Hescheler J ，Liang H ... -  《-》

Carbachol inhibits the L-type Ca2+ current augmented by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid in guinea pig ventricular myocytes: calcium-sensitivity hypothesis for muscarinic inhibition.

Shen JB ，Pappano AJ 《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》

Developmental changes in functional expression and beta-adrenergic regulation of I(f) in the heart of mouse embryo.

Song GL ，Tang M ，Liu CJ ，Luo HY ，Liang HM ，Hu XW ，Xi JY ，Gao LL ，Fleischmann B ，Hescheler J ... -  《-》

Muscarinic cholinergic regulation of L-type calcium channel in heart of embryonic mice at different developmental stages.

Liang HM ，Tang M ，Liu CJ ，Luo HY ，Song YL ，Hu XW ，Xi JY ，Gao LL ，Nie B ，Li SY ，Lai LL ，Hescheler J ... -  《-》

Modulation of L-type Ca(2+) channel current density and inactivation by beta-adrenergic stimulation during murine cardiac embryogenesis.

Nguemo F ，Sasse P ，Fleischmann BK ，Kamanyi A ，Schunkert H ，Hescheler J ，Reppel M ... -  《-》