Atrial fibrillation activates AMP-dependent protein kinase and its regulation of cellular calcium handling

• Verfasst von: Harada, Masahide [VerfasserIn]
• Verfasst von: Tadevosyan, Artavazd [VerfasserIn]
• Verfasst von: Qi, Xiaoyan [VerfasserIn]
• Verfasst von: Xiao, Jiening [VerfasserIn]
• Verfasst von: Liu, Tao [VerfasserIn]
• Verfasst von: Voigt, Niels [VerfasserIn]
• Verfasst von: Karck, Matthias [VerfasserIn]
• Verfasst von: Kamler, Markus [VerfasserIn]
• Verfasst von: Kodama, Itsuo [VerfasserIn]
• Verfasst von: Murohara, Toyoaki [VerfasserIn]
• Verfasst von: Dobrev, Dobromir [VerfasserIn]
• Verfasst von: Nattel, Stanley [VerfasserIn]
• Titel: Atrial fibrillation activates AMP-dependent protein kinase and its regulation of cellular calcium handling
• Titelzusatz: potential role in metabolic adaptation and prevention of progression
• Verf.angabe: Masahide Harada, Artavazd Tadevosyan, Xiaoyan Qi, Jiening Xiao, Tao Liu, Niels Voigt, Matthias Karck, Markus Kamler, Itsuo Kodama, Toyoaki Murohara, Dobromir Dobrev, Stanley Nattel
• E-Jahr: 2015
• Jahr: 29 June 2015
• Umfang: 12 S.
• Fussnoten: Gesehen am 13.07.2020
• Titel Quelle: Enthalten in: American College of CardiologyJournal of the American College of Cardiology
• Ort Quelle: New York, NY : Elsevier, 1983
• Jahr Quelle: 2015
• Band/Heft Quelle: 66(2015), 1, Seite 47-58
• ISSN Quelle: 1558-3597
• DOI: doi:10.1016/j.jacc.2015.04.056
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: cell calcium handling
• Sach-SW: heart pharmacology
• Sach-SW: myocardial energy metabolism
• K10plus-PPN: 1724505785

Abstract

Background - Atrial fibrillation (AF) is associated with metabolic stress, which activates adenosine monophosphate-regulated protein kinase (AMPK). - Objectives - This study sought to examine AMPK response to AF and associated metabolic stress, along with consequences for atrial cardiomyocyte Ca2+ handling. - Methods - Calcium ion (Ca2+) transients (CaTs) and cell shortening (CS) were measured in dog and human atrial cardiomyocytes. AMPK phosphorylation and AMPK association with Ca2+-handling proteins were evaluated by immunoblotting and immunoprecipitation. - Results - CaT amplitude and CS decreased at 4-min glycolysis inhibition (GI) but returned to baseline at 8 min, suggesting cellular adaptation to metabolic stress, potentially due to AMPK activation. GI increased AMPK-activating phosphorylation, and an AMPK inhibitor, compound C (CompC), abolished the adaptation of CaT and CS to GI. The AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) increased CaT amplitude and CS, restoring CompC-induced CaT and CS decreases. CompC decreased L-type calcium channel current (ICa,L), along with ICa,L-triggered CaT amplitude and sarcoplasmic reticulum (SR) Ca2+ content under voltage clamp conditions in dog cells and suppressed CaT and ICa,L in human cardiomyocytes. Small interfering ribonucleic acid-based AMPK knockdown decreased CaT amplitude in neonatal rat cardiomyocytes. L-type Ca2+ channel α subunits coimmunoprecipitated with AMPKα. Atrial AMPK-activating phosphorylation was enhanced by 1 week of electrically maintained AF in dogs; fractional AMPK phosphorylation was increased in paroxysmal AF and reduced in longstanding persistent AF patients. - Conclusions - AMPK is activated by metabolic stress and AF, and helps maintain the intactness of atrial ICa,L, Ca2+ handling, and cell contractility. AMPK contributes to the atrial compensatory response to AF-related metabolic stress; AF-related metabolic responses may be an interesting new therapeutic target.