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(Circulation Research. 2001;88:536.)
© 2001 American Heart Association, Inc.

Integrative Physiology

I_f Current and Spontaneous Activity in Mouse Embryonic Ventricular Myocytes

Kenji Yasui, Weiran Liu, Tobias Opthof, Kenji Kada, Jong-Kook Lee, Kaichiro Kamiya, Itsuo Kodama

From the Department of Circulation (K.Y., W.L., T.O., K. Kada, J.-K.L., K. Kamiya, I.K.), Division of Regulation of Organ Function, Research Institute of Environmental Medicine, Nagoya University, Japan and Department of Medical Physiology (T.O.), University Medical Center Utrecht, The Netherlands.

Correspondence to Kenji Yasui, MD, Department of Circulation, Division of Regulation of Organ Function, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. E-mail kenji{at}riem.nagoya-u.ac.jp

Abstract—Knowledge of the initiation of electrical and contractile activity in the embryonic heart relies to a large extent on data obtained in chicken. In recent years, molecular biological techniques have raised an interest in mouse physiology, including early embryonic development. We studied action potentials and the occurrence of one of the pacemaker currents, I_f, by the whole-cell voltage and current-clamp technique at the earliest stage at which a regular heartbeat is established (9.5 days postcoitum) and at 1 day before birth. We show, first, that at the early stage there is a prominent I_f in mouse embryonic ventricles, which decreases by 82% before birth in concert with the loss of regular spontaneous activity of ventricular cells. Second, the decrease in I_f current is associated with a slight change in channel gating kinetics and a decrease in total mRNA expression of the genes encoding for I_f current. Third, the most prevalent mRNA subtype is switched from HCN4 to HCN2 during the second half of embryonic development. Fourth, the I_f current may be modulated by the ß-adrenergic cascade, although the coupling to the ß-adrenoceptor in the sarcolemma itself is not yet mature. We conclude that I_f current of the sinus node type is present in early embryonic mouse ventricular cells. In association with a loss of I_f current, the ventricle tends to lose pacemaker potency during the second half of embryonic development.

Key Words: embryo • development • I_f current • HCN gene • ß-adrenoceptor modulation

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