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Electrical Conduction System Remodeling in Streptozotocin-Induced Diabetes Mellitus Rat Heart
Yu Zhang1,2, Yanwen Wang1, Joseph Yanni1
1Division of Cardiovascular Sciences, School of Medical Sciences, University of Manchester, Manchester, United Kingdom.
Insights
Type 1 diabetes mellitus (TIDM) causes cardiac conduction system (CCS) dysfunction, increasing arrhythmia risk. This study found significant protein changes in the diabetic rat heart, impacting electrical activity and potentially causing arrhythmias.
Area of Science:
- Cardiology
- Endocrinology
- Molecular Biology
Background:
- Cardiovascular complications, including arrhythmias, are prevalent in type 1 diabetes mellitus (TIDM).
- Previous in vivo studies demonstrated cardiac conduction system (CCS) dysfunction in diabetic rats, evidenced by decreased heart rate and prolonged QRS complex.
Purpose of the Study:
- To investigate the ex vivo function of the cardiac conduction system (CCS) in type 1 diabetes mellitus (TIDM).
- To identify alterations in key proteins regulating pacemaker mechanisms within the diabetic CCS.
Main Methods:
- Assessment of ex vivo cardiac electrophysiology, including RR interval, PR interval, and QRS duration.
- Measurement of sinoatrial node (SAN) beating rate and nodal cell properties (funny current density, cell capacitance).
- Quantitative analysis of CCS protein expression (HCN4, CaV channels, Cx channels, NCX1, RyR2) using Western blot.
Main Results:
- Diabetic rats exhibited significantly prolonged RR, PR intervals, and QRS duration.
- Isolated SAN preparations from diabetic rats showed a decreased beating rate.
- Significant reductions in key proteins (HCN4, CaV1.3, CaV3.1, Cx45, NCX1, RyR2, Cx40, Cx43) were observed in the diabetic CCS.
Conclusions:
- Type 1 diabetes mellitus (TIDM) induces complex functional and cellular changes in the cardiac conduction system (CCS).
- Altered expression of proteins crucial for action potential generation and propagation in the diabetic CCS is likely arrhythmogenic.
Abstract:
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.
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