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Basic Research in Cardiology

, Volume 100, Issue 1, pp 1–13 | Cite as

Ablation of Cav2.3 / E–type voltage–gated calcium channel results in cardiac arrhythmia and altered autonomic control within the murine cardiovascular system

  • Marco Weiergräber
  • Margit Henry
  • Michael Südkamp
  • Ernst-Rainer de Vivie
  • Jürgen Hescheler
  • Toni SchneiderEmail author
ORIGINAL CONTRIBUTION

Abstract

Voltage–gated calcium channels are key components in cardiac electrophysiology. We demonstrate that Cav2.3 is expressed in mouse and human heart and that mice lacking the Cav2.3 voltage–gated calcium channel exhibit severe alterations in cardiac function. Amplified cDNA fragments from murine heart and single cardiomyocytes reveal the expression of three different Cav2.3 splice variants. The ablation of Cav2.3 was found to be accompanied by a compensatory upregulation of the Cav3.1 T–type calcium channel, while other voltage–gated calcium channels remained unaffected. Telemetric ECG recordings from Cav2.3 deficient mice displayed subsidiary escape rhythm, altered atrial activation patterns, atrioventricular conduction disturbances and alteration in QRS–morphology. Furthermore, time domain analysis of heart rate variability (HRV) in Cav2.3(–|–) mice exhibited a significant increase in heart rate as well as in the coefficient of variance (CV) compared to control mice. Administration of atropin/propranolol revealed that increased heart rate was due to enhanced sympathetic tonus and that partial decrease of CV in Cav2.3(–|–) mice after autonomic block was in accordance with a complete abolishment of 2nd degree atrioventricular block. However, escape rhythms, atrial activation disturbances and QRS–dysmorphology remained unaffected, indicating that these are intrinsic cardiac features in Cav2.3(–|–) mice. We conclude that the expression of Cav2.3 is essential for normal impulse generation and conduction in murine heart.

Key words

R–type Ca2+–channel pacemaker conduction system 

Abbreviations

AP

action potential

Cav2.3

ion conducting α1 subunit of voltage–gated Ca2+ channels

CV

coefficient of variance

ES cells

embryonic stem cells

HPRT

hypoxanthin phosphoribosyltransferase

HRV

heart rate variability

PCS

pacemaker and conduction system

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Copyright information

© Steinkopff Verlag 2004

Authors and Affiliations

  • Marco Weiergräber
    • 1
    • 2
  • Margit Henry
    • 1
  • Michael Südkamp
    • 3
  • Ernst-Rainer de Vivie
    • 3
  • Jürgen Hescheler
    • 1
    • 2
  • Toni Schneider
    • 1
    • 2
    Email author
  1. 1.University of KölnInstitute of NeurophysiologyKölnGermany
  2. 2.Centre of Molecular Medicine Cologne (CMMC)University of KölnKölnGermany
  3. 3.Dept. of Cardiothoracic SurgeryUniversity of KölnKölnGermany

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