Developmental changes in functional expression and beta-adrenergic regulation of I(f) in the heart of mouse embryo.
The hyperpolarization-activated current (I(f)) plays an important role in determining the spontaneous rate of cardiac pacemaker cells. The automatic rhythmicity also exists in working cells of embryonic heart, therefore we studied developmental changes in functional expression and beta-adrenergic regulation of I(f) in embryonic mouse heart. The expression of I(f) is high in early developmental stage (EDS) (10.5 d after coitus) ventricular myocytes, low in intermediate developmental stage (IDS) (13.5 d) atrial or ventricular myocytes and even lower in late developmental stage (LDS) (16.5 d) atrial or ventricular myocytes, indicating that these cells of the EDS embryonic heart have some properties of pacemaker cells. Beta-adrenergic agonist isoproterenol (ISO) stimulates I(f) in LDS but not in EDS cardiomyocytes, indicating that the beta-adrenergic regulation of I(f) is not mature in EDS embryonic heart. But forskolin (a direct activator of adenylate cyclase) and 8-Br-cAMP (a membrane-permeable analogue of cAMP) increase the amplitude of I(f) in EDS cells, indicating that adenylate cyclase and cAMP function fairly well at early stage of development. Furthermore, the results demonstrate that I(f) is modulated by phosphorylation via cAMP dependent PKA both in EDS and LDS cells.
Song
Gui Li
GL
Department of Physiology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China.
Tang
Ming
M
Liu
Chang Jin
CJ
Luo
Hong Yan
HY
Liang
Hua Min
HM
Hu
Xin Wu
XW
Xi
Jiao Ya
JY
Gao
Lin Lin
LL
Fleischmann
Bernd
B
Hescheler
Jürgen
J
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000819:agonists / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004622:Embryo, Mammalian / Q000196:embryology* / Q000378:metabolism; D005260:Female; D006321:Heart / Q000196:embryology*; D006325:Heart Atria / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases