2-Aminoethoxydiphenyl borate, a inositol 1,4,5-triphosphate receptor inhibitor, prevents atrial fibrillation.
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.
Xiao
Junjie
J
Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Tongji University, 389 Xin Cun Road, Shanghai, China.
Liang
Dandan
D
Zhao
Hong
H
Liu
Ying
Y
Zhang
Hong
H
Lu
Xiaowei
X
Liu
Yi
Y
Li
Jun
J
Peng
Luying
L
Chen
Yi-Han
YH
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D001281:Atrial Fibrillation / Q000517:prevention & control*; D001896:Boron Compounds / Q000627:therapeutic use*; D002118:Calcium / Q000032:analysis; D002460:Cell Line; D004195:Disease Models, Animal; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D006321:Heart / Q000187:drug effects; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy; D009206:Myocardium / Q000737:chemistry; D011817:Rabbits
D001896:Boron Compounds; D005456:Fluorescent Dyes; D053496:Inositol 1,4,5-Trisphosphate Receptors; C049925:fura-2-am; D000255:Adenosine Triphosphate; C109986:2-aminoethoxydiphenyl borate; D002118:Calcium; D016257:Fura-2