Howarth F C, Chandler N J, Kharche S, Tellez J O, Greener I D, Yamanushi T T, Billeter R, Boyett M R, Zhang H, Dobrzynski H
Department of Physiology, United Arab Emirates University, Al Ain, United Arab Emirates.
Mol Cell Biochem. 2008 Dec;319(1-2):105-14. doi: 10.1007/s11010-008-9883-5. Epub 2008 Jul 16.
Abnormal QT prolongation with the associated arrhythmias is a significant predictor of mortality in diabetic patients. Gap junctional intercellular communication allows electrical coupling between heart muscle cells. The effects of streptozotocin (STZ)-induced diabetes mellitus on the expression and distribution of connexin 43 (Cx43) in ventricular muscle have been investigated. Cx43 mRNA expression was measured in ventricular muscle by quantitative PCR. The distribution of total Cx43, phosphorylated Cx43 (at serine 368) and non-phosphorylated Cx43 was measured in ventricular myocytes and ventricular muscle by immunocytochemistry and confocal microscopy. There was no significant difference in Cx43 mRNA between diabetic rat ventricle and controls. Total and phosphorylated Cx43 were significantly increased in ventricular myocytes and ventricular muscle and dephosphorylated Cx43 was not significantly altered in ventricular muscle from diabetic rat hearts compared to controls. Disturbances in gap junctional intercellular communication, which in turn may be attributed to alterations in balance between total, phosphorylated and dephosporylated Cx43, might partly underlie prolongation of QRS and QT intervals in diabetic heart.
异常QT间期延长及相关心律失常是糖尿病患者死亡率的重要预测指标。缝隙连接细胞间通讯可使心肌细胞实现电偶联。本研究探讨了链脲佐菌素（STZ）诱导的糖尿病对心室肌中连接蛋白43（Cx43）表达及分布的影响。采用定量PCR检测心室肌中Cx43 mRNA的表达。通过免疫细胞化学和共聚焦显微镜检测心室肌细胞和心室肌中总Cx43、磷酸化Cx43（丝氨酸368位点）和非磷酸化Cx43的分布。糖尿病大鼠心室与对照组之间Cx43 mRNA无显著差异。与对照组相比，糖尿病大鼠心脏的心室肌细胞和心室肌中总Cx43和磷酸化Cx43显著增加，而去磷酸化Cx43无显著变化。缝隙连接细胞间通讯紊乱，这反过来可能归因于总Cx43、磷酸化Cx43和去磷酸化Cx43之间平衡的改变，可能是糖尿病心脏QRS和QT间期延长的部分原因。
