Enhanced activity of inositol-1,4,5-trisphosphate receptors in atrial myocytes of atrial fibrillation patients

Abstract

The roles of inositol-1,4,5-trisphosphate receptors (IP3Rs) in arrhythmia are not fully understood, especially in human beings. Recently, the reported upregulated expression of IP3Rs in atrial myocytes of atrial fibrillation (AF) subjects suggested that IP3Rs might be associated with AF. To directly understand the roles of IP3Rs in AF, we have investigated the IP3R-dependent Ca2+ events as well as the cross-talk between IP3Rs and ryanodine receptors (RyRs) in permeabilized atrial myocytes of AF and normal sinus rhythm (NSR) patients by Ca2+ imaging. In the presence of tetracaine, IP(3)R-dependent Ca2+ events in AF atrial myocytes showed increased frequency, delayed termination and broadened width, compared with NSR myocytes. Moreover, when RyRs were not inhibited, IP3 or adenophostin induced an outburst of RyR-dependent spontaneous Ca2+ sparks with the altered spatial-temporal characteristics. The activation of IP3Rs also enhanced Ca2+ waves. These effects on RyR-dependent Ca2+ signaling were significantly stronger in AF myocytes than in NSR cells and were completely blocked by 2-aminoethoxydiphenyl borate. Thus, our results suggested not only an enhanced activity of IP3Rs but also an elevated cross-talk between IP3R- and RyR-mediated Ca2+ signaling in atrial myocytes of human AF patients, a reflection of altered function of IP3Rs in AF.