TY - JOUR
T1 - Electrical Conduction System Remodeling in Streptozotocin-Induced Diabetes Mellitus Rat Heart
AU - Zhang, Yu
AU - Wang, Yanwen
AU - Yanni, Joseph
AU - Qureshi, Mohammed Anwar
AU - Logantha, Sunil Jit R.J.
AU - Kassab, Sarah
AU - Boyett, Mark R.
AU - Gardiner, Natalie J.
AU - Sun, Hong
AU - Howarth, Frank Christopher
AU - Dobrzynski, Halina
N1 - Funding Information:
This study was supported by the British Heart Foundation (RG/11/18/29257), by the British Heart Foundation (PG/17/29/32945), and by the parents of YZ (Mr. Wei Zhang and Mrs. Jianming Yan).
Publisher Copyright:
© Copyright © 2019 Zhang, Wang, Yanni, Qureshi, Logantha, Kassab, Boyett, Gardiner, Sun, Howarth and Dobrzynski.
PY - 2019/7/8
Y1 - 2019/7/8
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 (SAN) 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 SAN; 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 (SAN) 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 SAN; 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.
KW - arrhythmias
KW - calcium handling protein
KW - cardiac conduction system
KW - gap junction channels
KW - ion channels
KW - remodeling
KW - type I diabetes
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U2 - 10.3389/fphys.2019.00826
DO - 10.3389/fphys.2019.00826
M3 - Article
AN - SCOPUS:85074656973
SN - 1664-042X
VL - 10
JO - Frontiers in Physiology
JF - Frontiers in Physiology
M1 - 826
ER -