Enhanced heterogeneity of myocardial conduction and severe cardiac electrical instability in annexin A7-deficient mice.
OBJECTIVE
Annexin A7 is involved in cardiomyocyte membrane organization and Ca(2+)-dependent signalling processes. We investigated the impact of annexin A7 on cardiac electrophysiological properties using an annexin A7-deficient mouse strain (annexin A7(-/-)).


METHODS
Nineteen adult annexin A7(-/-) and 14 wild-type mice were examined electrophysiologically in vivo by transvenous catheterization. Hearts were additionally perfused by the Langendorff method and epicardial activation mapping was performed.


RESULTS
The susceptibility to induction of atrial fibrillation was elevated in annexin A7(-/-) mice. Ten deficient animals showed atrial fibrillation (AF) episodes > or =1 min and sustained AF > or =30 min was observed in 4 annexin A7(-/-) mice, but in none of the wild-type mice. The incidence of ventricular tachycardia (VT) was higher in annexin A7(-/-) mice and VT duration was prolonged. Epicardial mapping showed elevated anisotropy and inhomogeneity of conduction, leading to conduction blocks in the deficient mice. Besides alterations of intracellular calcium homeostasis, electron microscopy showed a homogeneous, electron-dense material that filled the myocardial intercellular compartments and accumulated at the basement membranes. This led to expansion of the extracellular spaces, which was the most probable substrate factor responsible for the disturbances of electrical communication.


CONCLUSIONS
Annexin A7 deficiency causes severe electrical instability in the murine heart, including conduction disturbances and anisotropy of impulse propagation, which is accompanied by disturbed calcium handling and intercellular deposits.
Department of Medicine-Cardiology, University of Bonn, Germany. jan.schrickel@ukb.uni-bonn.de
Jan W
JW
Schrickel
Klara
K
Brixius
Claudia
C
Herr
Christoph S
CS
Clemen
Philipp
P
Sasse
Kathrin
K
Reetz
Christian
C
Grohé
Rainer
R
Meyer
Klaus
K
Tiemann
Rolf
R
Schröder
Wilhelm
W
Bloch
Georg
G
Nickenig
Bernd K
BK
Fleischmann
Angelika A
AA
Noegel
Robert H G
RH
Schwinger
Thorsten
T
Lewalter
D000818:Animals; D017310:Annexin A7 / Q000172:deficiency / Q000502:physiology*; D001281:Atrial Fibrillation / Q000209:etiology*; D018780:Body Surface Potential Mapping; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication; D004562:Electrocardiography; D006329:Heart Conduction System / Q000502:physiology*; D006706:Homeostasis; D051379:Mice; D008854:Microscopy, Electron; D032383:Myocytes, Cardiac / Q000648:ultrastructure; D010496:Pericardium; D017180:Tachycardia, Ventricular / Q000209:etiology*
D017310:Annexin A7; C480504:Anxa7 protein, mouse; D002118:Calcium