Bradycardia and Slowing of the Atrioventricular Conduction in Mice Lacking Ca V 3.1/α 1G T-Type Calcium Channels
- 9 June 2006
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 98 (11), 1422-1430
- https://doi.org/10.1161/01.res.0000225862.14314.49
Abstract
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/α1G T-type calcium channels (cacna1g) abolishes T-type calcium current (ICa,T) in isolated cells from the SAN and the atrioventricular node without affecting the L-type Ca2+ current (ICa,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 ICa,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.Keywords
This publication has 29 references indexed in Scilit:
- Serious workings of the funny currentProgress in Biophysics and Molecular Biology, 2006
- Physiology and pharmacology of the cardiac pacemaker (“funny”) currentPharmacology & Therapeutics, 2005
- Mouse Model of SCN5A -Linked Hereditary Lenègre’s DiseaseCirculation, 2005
- Structure‐function relationship in the AV junctionThe Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology, 2004
- Strategies to identify ion channel modulators: current and novel approaches to target neuropathic painDrug Discovery Today, 2004
- Functional Basis of Sinus Bradycardia in Congenital Heart BlockCirculation Research, 2004
- Functional Roles of Ca v 1.3 (α 1D ) Calcium Channel in Sinoatrial NodesCirculation Research, 2002
- Properties of the hyperpolarization-activated current (If) in isolated mouse sino-atrial cellsCardiovascular Research, 2001
- Lack of the Burst Firing of Thalamocortical Relay Neurons and Resistance to Absence Seizures in Mice Lacking α1G T-Type Ca2+ ChannelsNeuron, 2001
- Intracellular Ca2+ release contributes to automaticity in cat atrial pacemaker cellsThe Journal of Physiology, 2000