TY - JOUR
T1 - Electrical conduction system remodelling in streptozotocin-induced diabetes mellitus rat heart
AU - Zhang, Yu
AU - Wang, Yanwen
AU - Yanni Gerges, Joseph
AU - Quereshi, Mohammed Anwar
AU - Logantha, Sunil
AU - Al Adhamn, Sarah
AU - Boyett, Mark
AU - Gardiner, Natalie
AU - Sun, Hong
AU - Howarth, Frank Christoper
AU - Dobrzynski, Halina
PY - 2019
Y1 - 2019
N2 - Cardiovascular complications are common in type 1 diabetes mellitus (TIDM) and there is an increased risk of arrhythmias as a result of dysfunction of the cardiac conduction system (CCS). We have previously shown that, in vivo, there is a decrease in the heart rate and prolongation of the QRS complex in streptozotocin-induced type 1 diabetic rats indicating dysfunction of the CCS. The aim of this study was to investigate the function of the ex vivo CCS and key proteins that are involved in pacemaker mechanisms in TIDM. RR interval, PR interval and QRS complex duration were significantly increased in diabetic rats. The beating rate of the isolated sinoatrial node preparation was significantly decreased in diabetic rats. The funny current density and cell capacitance were significantly decreased in diabetic nodal cells. Western blot showed that proteins involved in the function of the CCS were significantly decreased in diabetic rats, namely: HCN4, Cav1.3, Cav3.1, Cx45 and NCX1 in the sinoatrial node; RyR2 and NCX1 in the atrioventricular junction and Cx40, Cx43, Cx45 and RyR2 in the Purkinje network. We conclude that there are complex functional and cellular changes in the CCS in TIDM. The changes in the proteins involved in the function of this electrical system are expected to adversely affect action potential generation and propagation, and these changes are likely to be arrhythmogenic.
AB - Cardiovascular complications are common in type 1 diabetes mellitus (TIDM) and there is an increased risk of arrhythmias as a result of dysfunction of the cardiac conduction system (CCS). We have previously shown that, in vivo, there is a decrease in the heart rate and prolongation of the QRS complex in streptozotocin-induced type 1 diabetic rats indicating dysfunction of the CCS. The aim of this study was to investigate the function of the ex vivo CCS and key proteins that are involved in pacemaker mechanisms in TIDM. RR interval, PR interval and QRS complex duration were significantly increased in diabetic rats. The beating rate of the isolated sinoatrial node preparation was significantly decreased in diabetic rats. The funny current density and cell capacitance were significantly decreased in diabetic nodal cells. Western blot showed that proteins involved in the function of the CCS were significantly decreased in diabetic rats, namely: HCN4, Cav1.3, Cav3.1, Cx45 and NCX1 in the sinoatrial node; RyR2 and NCX1 in the atrioventricular junction and Cx40, Cx43, Cx45 and RyR2 in the Purkinje network. We conclude that there are complex functional and cellular changes in the CCS in TIDM. The changes in the proteins involved in the function of this electrical system are expected to adversely affect action potential generation and propagation, and these changes are likely to be arrhythmogenic.
U2 - 10.3389/fphys.2019.00826
DO - 10.3389/fphys.2019.00826
M3 - Article
SN - 1664-042X
VL - 10
SP - 1
JO - Frontiers in Physiology
JF - Frontiers in Physiology
M1 - 826
ER -