Reduction in dynamin-2 is implicated in ischaemic cardiac arrhythmias.
Ischaemic cardiac arrhythmias cause a large proportion of sudden cardiac deaths worldwide. The ischaemic arrhythmogenesis is primarily because of the dysfunction and adverse remodelling of sarcolemma ion channels. However, the potential regulators of sarcolemma ion channel turnover and function in ischaemic cardiac arrhythmias remains unknown. Our previous studies indicate that dynamin-2 (DNM2), a cardiac membrane-remodelling GTPase, modulates ion channels membrane trafficking in the cardiomyocytes. Here, we have found that DNM2 plays an important role in acute ischaemic arrhythmias. In rat ventricular tissues and primary cardiomyocytes subjected to acute ischaemic stress, the DNM2 protein and transcription levels were markedly down-regulated. This DNM2 reduction was coupled with severe ventricular arrhythmias. Moreover, we identified that the down-regulation of DNM2 within cardiomyocytes increases the action potential amplitude and prolongs the re-polarization duration by depressing the retrograde trafficking of Nav1.5 and Kir2.1 channels. These effects are likely to account for the DNM2 defect-induced arrhythmogenic potentials. These results suggest that DNM2, with its multi-ion channel targeting properties, could be a promising target for novel antiarrhythmic therapies.
['Shi|Dan|D|', 'Xie|Duanyang|D|', 'Zhang|Hong|H|', 'Zhao|Hong|H|', 'Huang|Jian|J|', 'Li|Changming|C|', 'Liu|Yi|Y|', 'Lv|Fei|F|', 'The|Erlinda|E|', 'Liu|Yuan|Y|', 'Yuan|Tianyou|T|', 'Wang|Shiyi|S|', 'Chen|Jinjin|J|', 'Pan|Lei|L|', 'Yu|Zuoren|Z|', 'Liang|Dandan|D|', 'Zhu|Weidong|W|', 'Zhang|Yuzhen|Y|', 'Li|Li|L|', 'Peng|Luying|L|', 'Li|Jun|J|', 'Chen|Yi-Han|YH|']
D000818:Animals D001145:Arrhythmias, Cardiac D019921:Biotinylation D015153:Blotting, Western D002478:Cells, Cultured D034285:Dynamin II D004562:Electrocardiography D004594:Electrophysiology D007124:Immunoenzyme Techniques D007511:Ischemia D008297:Male D032383:Myocytes, Cardiac D062554:NAV1.5 Voltage-Gated Sodium Channel D024661:Potassium Channels, Inwardly Rectifying D012333:RNA, Messenger D051381:Rats D017207:Rats, Sprague-Dawley D060888:Real-Time Polymerase Chain Reaction D020133:Reverse Transcriptase Polymerase Chain Reaction
dynamin-2 ischaemic cardiac arrhythmias ion channels Nav1.5 Kir2.1