摘要：SummaryAtrial fibrillation (AF), the most common abnormal heart rhythm, is a major cause for stroke. Aging is a significant risk factor for AF; however, specific ionic pathways that can elucidate how aging leads to AF remain elusive. We used young and old wild-type and PKC epsilon- (PKCϵ) knockout mice, whole animal, and cellular electrophysiology, as well as whole heart, and cellular imaging to investigate how aging leads to the aberrant functioning of a potassium current, and consequently to AF facilitation. Our experiments showed that knocking out PKCϵ abrogates the effects of aging on AF by preventing the development of a constitutively active acetylcholine sensitive inward rectifier potassium current (IKACh). Moreover, blocking this abnormal current in the old heart reduces AF inducibility. Our studies demonstrate that in the aging heart, IKAChis constitutively active in a PKCϵ-dependent manner, contributing to the perpetuation of AF.Graphical abstractDisplay OmittedHighlights•Atrial fibrillation (AF) is highly prevalent in aging and is a major cause of stroke•A potassium current (IKACh) is aberrantly active in atrial myocytes from aged hearts•Knocking out PKCε prevents the development of this aberrant current•Blocking IKAChor knocking out PKCε abrogates the effects of aging on AFBiological sciences; Animal physiology; Proteomics; Transcriptomics
