Functional role of TASK-1 in the heart: studies in TASK-1-deficient mice show prolonged cardiac repolarization and reduced heart rate variability.
TASK-1, a member of the recently identified K2P channel family, is mainly expressed in the heart and the nervous system. TASK-1 is regulated by several physiological and pathological conditions and functions as a background potassium channel. However, there are limited data concerning the significance of TASK-1 in cardiac physiology. We studied the functional role of TASK-1 in the heart by cardiac phenotyping the TASK-1-deficient mouse (TASK-1(-/-)). TASK-1 was predominantly expressed in the ventricles of control animals. Real-time PCR and immunoblot demonstrated that the expression of seven other K2P channels was unchanged in TASK-1(-/-) mice. No structural or functional abnormalities were found by histology and echocardiography. Electrophysiological studies recording monophasic action potentials (MAPs) showed a significant prolongation of action potential duration in spontaneously beating and atrially paced hearts, respectively. Surface ECGs of TASK-1(-/-) mice revealed a significant prolongation of the rate corrected QT interval. Telemetric ECG recordings for 24 h, during physical and pharmacological stress testing and after ischemia/reperfusion injury did not result in a higher incidence of arrhythmias. Infarct size was comparable in both genotypes. However, TASK-1(-/-) mice had a higher mean heart rate and significantly reduced heart rate variability (HRV). Time and frequency domain measurements as well as baroreceptor reflex testing revealed a sympathovagal imbalance with a shift to an increase in sympathetic influence in TASK-1(-/-) mice. In conclusion, TASK-1 plays a functional role in the repolarization of the cardiac action potential in vivo and contributes to the maintenance of HRV.
Donner
Birgit C
BC
Department of Pediatric Cardiology and Pneumology, University Children's Hospital, Moorenstrasse 5, 40225 Düsseldorf, Germany. birgit.donner@med.uni-duesseldorf.de
Schullenberg
Martina
M
Geduldig
Nora
N
Hüning
Anja
A
Mersmann
Jan
J
Zacharowski
Kai
K
Kovacevic
Alexander
A
Decking
Ulrich
U
Aller
Maria Isabel
MI
Schmidt
Klaus G
KG
D000200:Action Potentials; D000818:Animals; D006321:Heart / Q000502:physiology; D006329:Heart Conduction System / Q000502:physiology; D006334:Heart Function Tests; D006339:Heart Rate; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009929:Organ Size; D010641:Phenotype; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D013686:Telemetry; D018879:Ventricular Premature Complexes / Q000235:genetics
D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3