Atrial Natriuretic Peptide Regulates Ca2 Channel in Early Developmental CardiomyocytesReport as inadecuate

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Cardiomyocytes derived from murine embryonic stem ES cells possess various membrane currents and signaling cascades link to that of embryonic hearts. The role of atrial natriuretic peptide ANP in regulation of membrane potentials and Ca2+ currents has not been investigated in developmental cardiomyocytes.

Methodology-Principal Findings

We investigated the role of ANP in regulating L-type Ca2+ channel current ICaL in different developmental stages of cardiomyocytes derived from ES cells. ANP decreased the frequency of action potentials APs in early developmental stage EDS cardiomyocytes, embryonic bodies EB as well as whole embryo hearts. ANP exerted an inhibitory effect on basal ICaL in about 70% EDS cardiomyocytes tested but only in about 30% late developmental stage LDS cells. However, after stimulation of ICaL by isoproterenol ISO in LDS cells, ANP inhibited the response in about 70% cells. The depression of ICaL induced by ANP was not affected by either Nω, Nitro-L-Arginine methyl ester L-NAME, a nitric oxide synthetase NOS inhibitor, or KT5823, a cGMP-dependent protein kinase PKG selective inhibitor, in either EDS and LDS cells; whereas depression of ICaL by ANP was entirely abolished by erythro-9-2-Hydroxy-3-nonyl adenine EHNA, a selective inhibitor of type 2 phosphodiesterasePDE2 in most cells tested.


Taken together, these results indicate that ANP induced depression of action potentials and ICaL is due to activation of particulate guanylyl cyclase GC, cGMP production and cGMP-activation of PDE2 mediated depression of adenosine 3′, 5′–cyclic monophophate cAMP–cAMP-dependent protein kinase PKA in early cardiomyogenesis.

Author: Lin Miao, Min Wang, Wen-Xuan Yin, Qi Yuan, Ying-Xiao Chen, Bernd Fleischmann, Jürgen Hescheler , Guangju Ji



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