Bradycardia and slowing of the atrioventricular conduction in mice lacking CaV3.1/alpha1G T-type calcium channels

Circ Res. 2006 Jun 9;98(11):1422-30. doi: 10.1161/01.RES.0000225862.14314.49. Epub 2006 May 11.

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/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrioventricular Node / metabolism
  • Atrioventricular Node / pathology
  • Atrioventricular Node / physiopathology*
  • Bradycardia / etiology*
  • Bradycardia / metabolism
  • Bradycardia / pathology
  • Bradycardia / physiopathology*
  • Calcium Channels, T-Type / deficiency*
  • Electric Conductivity
  • Electrocardiography
  • Electrophysiology
  • Heart Rate
  • Hypnotics and Sedatives / pharmacology
  • Mice
  • Mice, Knockout
  • Protein Isoforms / deficiency
  • Sinoatrial Node / physiopathology

Substances

  • Cacna1g protein, mouse
  • Calcium Channels, T-Type
  • Hypnotics and Sedatives
  • Protein Isoforms