Yasui et al Automaticity and I f in Mouse Embryo

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 prominentI 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 b-adrenergic cascade, although the coupling to the b-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. (Circ Res. 2001;88:536-542.)