2-Aminoethoxydiphenyl borate, a inositol 1,4,5-triphosphate receptor inhibitor, prevents atrial fibrillation

Abstract

The expression of the inositol 1,4,5-triphosphate receptor (IP3R) is upregulated and the function of IP3R also increases during atrial fibrillation (AF). 2-Aminoethoxydiphenyl borate (2-APB) is a membrane-permeable inhibitor of IP3R. However, the effect of 2-APB on AF is unknown. The aim of the present study is to explore the effects of 2-APB on AF. In vitro rabbit heart models of ischemia-, stretch- and cholinergic agitation-induced AF were developed. Fura-2-acetoxymethyl (Fura-2-AM) and Mg2+-Fura-2-AM were used to monitor alterations of intracellular Ca2+ and ATP, respectively, in HL-1 cells, an atrial muscle cell line, under chemical ischemia or cholinergic agitation. The results showed that inhibition of IP3R significantly reduced the incidence and its probability of being sustained in all three types of AF. IP3R inhibition ameliorated the cytoplasmic Ca2+ overload and energy compromise resulting from chemical ischemia or cholinergic agitation. Thus, IP3R inhibition may be a novel target for AF treatment, and IP3R may be an important molecule in the context of different kinds of AF.