Effects Of ITPR1 Gene On Cardiac Function In Zebrafish

Atrial fibrillation is a kind of arrhythmia, which is very common in clinics. With a variety of risk factors appearing, such as age, obesity, high blood pressure, the prevalence of atrial fibrillation increased. Atrial fibrillation causes a large number of morbidity and mortality, especially increases the risk of high blood pressure and stroke. In addition to the traditional risk factors, genetic factors have also been shown to contribute to the occurrence of atrial fibrillation.Atrial fibrillation is mainly divided into electrical remodeling and structural remodeling. The electrical remodeling mainly refers to abnormal cycle of Na⁺, K⁺ and Ca²⁺ in heart. The occurrence of atrial fibrillation has a substantial genetic basis, which is considered to be an autosomal dominant inheritance. Mutation of RyR2 gene is associated with stresses induced ventricular tachycardia and right ventricular dysplasia. ITPR1 gene encode inositol 1, 4, 5-trisphosphate receptor type 1, which is a ligand gated ion channel protein that mediates Ca2+ release from the endoplasmic reticulum liking the RyR2 receptor. We speculated that the down regulation of ITPR1 gene will cause a decrease of inositol 1, 4, 5-trisphosphate receptor type 1, and influence the transportation of calcium,leading to the occurrence of atrial fibrillation eventually.In order to explore the role of ITPR1 gene in zebrafish heart development, we studied the expression of ITPR1 gene in different stages of zebrafish embryonic development using the whole in situ hybridization, finding the gene existed in various stages of embryonic development. We used Morpholino（MO）, which can block gene function. The changes of cardiac phenotype were observed by in situ hybridization experiment. The results show that cardiac precursor cells weakened or disappeared in the anterior lateral mesoderm on GATA4 expression region, while down regulation of ITPR1 a gene can cause cardiac abnormal cardiac looping in zebrafish. We speculated that the ITPR1 a gene plays an important role in the development of the heart in the early stage of the development of the embryo. By analyzing the heart rate of zebrafish, it was found that ITPR1 down regulation could lead to the increase of heart rate. Finally, the regulatory effect of ITPR1 on ion channel related genes SCN5 A, HCN4, Cav1.3 and KCNJ2 geneswas determined by fluorescence quantitative PCR reaction.In this study, the effect of ITPR1 a gene on the development of the heart of zebrafish has an important role in understanding the mechanism of the occurrence of atrial fibrillation, which provides a basis for the treatment of atrial fibrillation.