Knowledge of the initiation of electrical and contractile activity in the e
mbryonic heart relies to a large extent on data obtained in chicken. In rec
ent years, molecular biological techniques have raised an interest in mouse
physiology, including early embryonic development. We studied action poten
tials and the occurrence of one of the pacemaker currents, I-f, by the whol
e-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 encod
ing for I-f current. Third, the most prevalent mRNA subtype is switched fro
m HCN4 to HCN2 during the second half of embryonic development. Fourth, the
I-f current may be modulated by the beta -adrenergic cascade, although the
coupling to the beta -adrenoceptor in the sarcolemma itself is not yet mat
ure. We conclude that I-f current of the sinus node type is present in earl
y embryonic mouse ventricular cells. In association with a loss of I-f curr
ent, the ventricle tends to lose pacemaker potency during the second half o
f embryonic development.