Bradycardia and slowing of the atrioventricular conduction in mice lacking CaV3.1/alpha1G T-type calcium channels.
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 CaV3.1/alpha1G 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 Ca2+ 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 CaV3.1(-/-) 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 CaV3.1/T-type Ca2+ channels contribute to SAN pacemaker activity and atrioventricular conduction.
Mangoni
Matteo E
ME
Institut de Génomique Fonctionnelle, CNRS UMR5203-INSERM U661, Département de Physiologie, Université de Montpellier I, Montpellier cedex 05, F-34094, France. matteo.mangoni@igf.cnrs.fr
Traboulsie
Achraf
A
Leoni
Anne-Laure
AL
Couette
Brigitte
B
Marger
Laurine
L
Le Quang
Khai
K
Kupfer
Elodie
E
Cohen-Solal
Anne
A
Vilar
José
J
Shin
Hee-Sup
HS
Escande
Denis
D
Charpentier
Flavien
F
Nargeot
Joël
J
Lory
Philippe
P
D000818:Animals; D001283:Atrioventricular Node / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001919:Bradycardia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020747:Calcium Channels, T-Type / Q000172:deficiency*; D004553:Electric Conductivity; D004562:Electrocardiography; D004594:Electrophysiology; D006339:Heart Rate; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000172:deficiency; D012849:Sinoatrial Node / Q000503:physiopathology
C498197:Cacna1g protein, mouse; D020747:Calcium Channels, T-Type; D006993:Hypnotics and Sedatives; D020033:Protein Isoforms