Pannexin-1 Deficient Mice Have an Increased Susceptibility for Atrial Fibrillation and Show a QT-Prolongation Phenotype
Autor: | Sofia Klein, Stella Petric, Tillman Lahres, Zhaoping Ding, Lisa Dannenberg, Birgit C. Donner, Lukas Clasen, Klaus Schmidt |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Physiology Stimulation Context (language use) Nerve Tissue Proteins QT prolongation QT interval lcsh:Physiology Intracardiac injection Connexins lcsh:Biochemistry 03 medical and health sciences Mice Heart Rate Internal medicine Heart rate Atrial Fibrillation medicine Animals lcsh:QD415-436 Heart Atria In vivo electrophysiology Mice Knockout Cardiac repolarization lcsh:QP1-981 Cardiac electrophysiology business.industry Pannexin-1 Atrial fibrillation Heart medicine.disease Cardiac ion channels Electrophysiological Phenomena Mice Inbred C57BL Electrophysiology Knock-out 030104 developmental biology Cardiology business |
Zdroj: | Cellular Physiology and Biochemistry, Vol 38, Iss 2, Pp 487-501 (2016) |
ISSN: | 1421-9778 |
Popis: | Background/Aims: Pannexin-1 (Panx1) is an ATP release channel that is ubiquitously expressed and coupled to several ligand-gated receptors. In isolated cardiac myocytes, Panx1 forms large conductance channels that can be activated by Ca2+ release from the sarcoplasmic reticulum. Here we characterized the electrophysiological function of these channels in the heart in vivo, taking recourse to mice with Panx1 ablation. Methods: Cardiac phenotyping of Panx1 knock-out mice (Panx1-/-) was performed by employing a molecular, cellular and functional approach, including echocardiography, surface and telemetric ECG recordings with QT analysis, physical stress testing and quantification of heart rate variability. In addition, an in vivo electrophysiological study entailed programmed electrical stimulation using an intracardiac octapolar catheter. Results: Panx1 deficiency results in a higher incidence of AV-block, delayed ventricular depolarisation, significant prolongation of QT- and rate corrected QT-interval and a higher incidence of atrial fibrillation after intraatrial burst stimulation. Conclusion: Panx1 seems to play an important role in murine cardiac electrophysiology and warrants further consideration in the context of hereditary forms of atrial fibrillation. |
Databáze: | OpenAIRE |
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