Publication Date

9-22-2020

Journal

Circulation

DOI

10.1161/CIRCULATIONAHA.120.045791

PMID

32683896

PMCID

PMC7508800

PubMedCentral® Posted Date

9-22-2021

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Animals, Atrial Fibrillation, Calcium Signaling, Female, Humans, Male, Mice, Mice, Knockout, Muscle Proteins, Myocardium, Myosin-Light-Chain Kinase, Phosphorylation, Protein Serine-Threonine Kinases, Ryanodine Receptor Calcium Release Channel, Sarcoplasmic Reticulum

Abstract

BACKGROUND: Enhanced diastolic calcium (Ca

METHODS: Western blotting was performed with right atrial biopsies from patients with paroxysmal AF. SPEG atrial knockout mice were generated using adeno-associated virus 9. In mice, AF inducibility was determined using intracardiac programmed electric stimulation, and diastolic Ca

RESULTS: Western blotting revealed decreased SPEG protein levels in atrial biopsies from patients with paroxysmal AF in comparison with patients in sinus rhythm. SPEG atrial-specific knockout mice exhibited increased susceptibility to pacing-induced AF by programmed electric stimulation and enhanced Ca

CONCLUSIONS: Unlike other kinases (PKA, CaMKII) that increase RyR2 activity, SPEG phosphorylation reduces RyR2-mediated sarcoplasmic reticulum Ca

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