Résumé
The generation of the mammalian heartbeat is a complex and vital function requiring multiple and coordinated ionic channel activities. The functional role of low-voltage activated (LVA) T-type calcium channels in the pacemaker activity of the sinoatrial node (SAN) is, to date, unresolved. Here we show that disruption of the gene coding for Ca
v
3.1/α
1G
T-type calcium channels (
cacna1g
) abolishes T-type calcium current (
I
Ca,T
) in isolated cells from the SAN and the atrioventricular node without affecting the L-type Ca
2+
current (
I
Ca,L
). By using telemetric electrocardiograms on unrestrained mice and intracardiac recordings, we find that
cacna1g
inactivation causes bradycardia and delays atrioventricular conduction without affecting the excitability of the right atrium. Consistently, no
I
Ca,T
was detected in right atrium myocytes in both wild-type and Ca
v
3.1
−/−
mice. Furthermore, inactivation of
cacna1g
significantly slowed the intrinsic in vivo heart rate, prolonged the SAN recovery time, and slowed pacemaker activity of individual SAN cells through a reduction of the slope of the diastolic depolarization. Our results demonstrate that Ca
v
3.1/T-type Ca
2+
channels contribute to SAN pacemaker activity and atrioventricular conduction.