IKACH IS CONSTITUTIVELY ACTIVE VIA PKC EPSILON IN AGING MEDIATED ATRIAL FIBRILLATION

Atrial fibrillation (AF), the most common abnormal heart rhythm, is a major cause for stroke. Aging is the greatest 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 (WT) and PKC epsilon (PKCepsilon) knockout (KO) 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 PKC epsilon 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 prevents AF inducibility. Our studies demonstrate that in the aging heart, IKACh is constitutively active in a PKC epsilon dependent manner, contributing to the perpetuation of AF