Ablation of Ca(v)2.3 / E-type voltage-gated calcium channel results in cardiac arrhythmia and altered autonomic control within the murine cardiovascular system.
Voltage-gated calcium channels are key components in cardiac electrophysiology. We demonstrate that Ca(v)2.3 is expressed in mouse and human heart and that mice lacking the Ca(v)2.3 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 Ca(v)2.3 splice variants. The ablation of Ca(v)2.3 was found to be accompanied by a compensatory upregulation of the Ca(v)3.1 T-type calcium channel, while other voltage-gated calcium channels remained unaffected. Telemetric ECG recordings from Ca(v)2.3 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 Ca(v)2.3(-/-) 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 Ca(v)2.3(-/-) mice after autonomic block was in accordance with a complete abolishment of 2(nd) degree atrioventricular block. However, escape rhythms, atrial activation disturbances and QRS-dysmorphology remained unaffected, indicating that these are intrinsic cardiac features in Ca(v)2.3(-/-) mice. We conclude that the expression of Ca(v)2.3 is essential for normal impulse generation and conduction in murine heart.
Weiergräber
Marco
M
University of Köln, Institute of Neurophysiology, Robert-Koch-Str. 39, 50931, Köln, Germany.
Henry
Margit
M
Südkamp
Michael
M
de Vivie
Ernst-Rainer
ER
Hescheler
Jürgen
J
Schneider
Toni
T
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D001340:Autonomic Nerve Block; D001341:Autonomic Nervous System / Q000503:physiopathology*; D015220:Calcium Channels / Q000502:physiology*; D002319:Cardiovascular System / Q000503:physiopathology*; D004562:Electrocardiography; D051379:Mice; D008810:Mice, Inbred C57BL
D015220:Calcium Channels