REGULAR ARTICLES

Cell Research (2002); 12(5-6):385-394

Developmental changes in functional expression and b-adrenergic regulation of I_f in the heart of mouse embryo

Gui Li SONG¹, Ming TANG^1,*, Chang Jin LIU¹, Hong Yan LUO¹, Hua Min LIANG¹, Xin Wu HU¹, JiaoYa XI¹, Lin Lin GAO¹, Bernd FLEISCHMANN², J¨1rgen HESCHELER²

¹Department of Physiology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China
²Institute of Neurophysiology, University of Cologne, D-50931 Cologne, Germany

Received Jun-3-2002 Revised Oct-8-2002 Accepted Oct-24-2002

Correspondence: Prof. Ming TANG Department of Physiology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China Tel: 0086-27-83692622,   0086-27-83639950, E-mail: tangming49@hotmail.com

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Abstract

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 b-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. b-adrenergic agonist isoproterenol (ISO) stimulates I_f in LDS but not in EDS cardiomyocytes, indicating that the b-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.

Key words: embryonic cardiomyocyte, development, I_f, b-adrenergic.