標題: | Roles of impaired intracellular calcium cycling in arrhythmogenicity of diabetic mouse model |
作者: | Chou, Chung-Chuan Ho, Chien-Te Lee, Hui-Ling Chu, Yen Yen, Tzung-Hai Wen, Ming-Shien Lin, Shien-Fong Lee, Cheng-Hung Chang, Po-Cheng 分子醫學與生物工程研究所 Institute of Molecular Medicine and Bioengineering |
關鍵字: | arrhythmia;conduction velocity;db/db mouse;intracellular calcium dynamics;type 2 diabetes |
公開日期: | 1-十月-2017 |
摘要: | BackgroundDiabetes mellitus is associated an increased risk of ventricular arrhythmias (VAs), but the underlying electrophysiological mechanisms are not fully explored. This study was aimed to test whether dynamic factors and Ca-i handling play roles in arrhythmogenesis of a diabetic animal model. Methods: We used 26 db/db type 2 diabetes mice and 28 control mice in this study. VA inducibility was evaluated in vivo under isoflurane general anesthesia. The intracellular Ca2+ (Ca-i) and membrane voltage (V-m) signals of the Langendorff-perfused mouse hearts were simultaneously recorded using the optical mapping technique. Action potential duration (APD), Ca-i dynamics conduction velocity (CV), and arrhythmogenic alternans were analyzed. Western blot was conducted to examine expressions of calcium handling and associated ion channels proteins. Results: The diabetic db/db mice showed significantly increased VA inducibility and severity. Longer APD and Ca-i transient duration and slower Ca-i decay and CV in the db/db mice than these in the control ones were observed. Dynamic pacing showed increased incidence of spatially discordant alternans leading to more VA inducibility in the db/db mice. Western blot analyses revealed increased phosphorylated-Ca2+/calmodulin-dependent protein kinase II protein expression and decreased ryanodine receptor protein expression, which probably underlay the molecular mechanisms of enhanced arrhythmogenicity in db/db mice. Conclusions: The type 2 diabetic mouse hearts show impaired repolarization, Ca-i handling homeostasis, and cardiac conduction reserve, leading to vulnerability of spatially discordant alternans development and induction of VA. Altered Ca-i-handling protein expressions probably underlie the molecular mechanisms of arrhythmogenicity in the type 2 diabetes animal model. |
URI: | http://dx.doi.org/10.1111/pace.13166 http://hdl.handle.net/11536/143956 |
ISSN: | 0147-8389 |
DOI: | 10.1111/pace.13166 |
期刊: | PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY |
Volume: | 40 |
起始頁: | 1087 |
結束頁: | 1095 |
顯示於類別: | 期刊論文 |