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Functional role of TASK-1 in the heart: studies in TASK-1-deficient mice show prolonged cardiac repolarization and reduced heart rate variability

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Abstract

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.

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Abbreviations

TWIK:

Tandem pore domain weak inward rectifying K+ channel

TASK:

TWIK related acid-sensitive K+ channel

TREK:

TWIK related K+ channel

RRU:

Relative RNA unit

AR:

Area at risk

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Acknowledgments

The TASK-1−/− mouse was supplied by Dr. W. Wisden from the Department of Clinical Neurobiology, University of Heidelberg. Dr. Sager and Dr. Engelhardt, Animal Care Facility Duesseldorf, are acknowledged for their encouraging help with the animal experiments. The work was supported by two grants from the University Duesseldorf and by the German Society for Pediatric Cardiology. MS was a recipient of “Forschungsförderung der Universität Düsseldorf”.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pediatric Cardiology and Pneumology, University Children′s Hospital, Moorenstrasse 5, 40225, Düsseldorf, Germany

    Birgit C. Donner, Martina Schullenberg, Nora Geduldig, Anja Hüning, Alexander Kovacevic & Klaus G. Schmidt

  2. Clinic of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt, Germany

    Jan Mersmann & Kai Zacharowski

  3. Department of Cardiovascular Physiology, Heinrich Heine University Düesseldorf, Düsseldorf, Germany

    Ulrich Decking

  4. Department of Clinical Neurobiology, University of Heidelberg, Heidelberg, Germany

    Maria Isabel Aller

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  1. Birgit C. Donner
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Correspondence to Birgit C. Donner.

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Donner, B.C., Schullenberg, M., Geduldig, N. et al. Functional role of TASK-1 in the heart: studies in TASK-1-deficient mice show prolonged cardiac repolarization and reduced heart rate variability. Basic Res Cardiol 106, 75–87 (2011). https://doi.org/10.1007/s00395-010-0128-x

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