The Pattern of mRNA Expression Is Changed in Sinoatrial Node from Goto-Kakizaki Type 2 Diabetic Rat Heart

Background. In vivo experiments in Goto-Kakizaki (GK) type 2 diabetic rats have demonstrated reductions in heart rate from a young age. The expression of genes encoding more than 70 proteins that are associated with the generation and conduction of electrical activity in the GK sinoatrial node (SAN)...

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Main Authors: F. C. Howarth, M. A. Qureshi, P. Jayaprakash, K. Parekh, M. Oz, H. Dobrzynski, T. E. Adrian
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2018/8454078
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author F. C. Howarth
M. A. Qureshi
P. Jayaprakash
K. Parekh
M. Oz
H. Dobrzynski
T. E. Adrian
author_facet F. C. Howarth
M. A. Qureshi
P. Jayaprakash
K. Parekh
M. Oz
H. Dobrzynski
T. E. Adrian
author_sort F. C. Howarth
collection DOAJ
description Background. In vivo experiments in Goto-Kakizaki (GK) type 2 diabetic rats have demonstrated reductions in heart rate from a young age. The expression of genes encoding more than 70 proteins that are associated with the generation and conduction of electrical activity in the GK sinoatrial node (SAN) have been evaluated to further clarify the molecular basis of the low heart rate. Materials and Methods. Heart rate and expression of genes were evaluated with an extracellular electrode and real-time RT-PCR, respectively. Rats aged 12-13 months were employed in these experiments. Results. Isolated spontaneous heart rate was reduced in GK heart (161 ± 12 bpm) compared to controls (229 ± 11 bpm). There were many differences in expression of mRNA, and some of these differences were of particular interest. Compared to control SAN, expression of some genes were downregulated in GK-SAN: gap junction, Gja1 (Cx43), Gja5 (Cx40), Gjc1 (Cx45), and Gjd3 (Cx31.9); cell membrane transport, Trpc1 (TRPC1) and Trpc6 (TRPC6); hyperpolarization-activated cyclic nucleotide-gated channels, Hcn1 (HCN1) and Hcn4 (HCN4); calcium channels, Cacna1d (Cav1.3), Cacna1g (Cav3.1), Cacna1h (Cav3.2), Cacna2d1 (Cavα2δ1), Cacna2d3 (Cavα2δ3), and Cacng4 (Cavγ4); and potassium channels, Kcna2 (Kv1.2), Kcna4 (Kv1.4), Kcna5 (Kv1.5), Kcnb1 (Kv2.1), Kcnd3 (Kv4.3), Kcnj2 (Kir2.1), Kcnk1 (TWIK1), Kcnk5 (K2P5.1), Kcnk6 (TWIK2), and Kcnn2 (SK2) whilst others were upregulated in GK-SAN: Ryr2 (RYR2) and Nppb (BNP). Conclusions. This study provides new insight into the changing expression of genes in the sinoatrial node of diabetic heart.
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spelling doaj-art-9b974661a29c4837b62ae7d10c5ea16e2025-02-03T01:00:26ZengWileyJournal of Diabetes Research2314-67452314-67532018-01-01201810.1155/2018/84540788454078The Pattern of mRNA Expression Is Changed in Sinoatrial Node from Goto-Kakizaki Type 2 Diabetic Rat HeartF. C. Howarth0M. A. Qureshi1P. Jayaprakash2K. Parekh3M. Oz4H. Dobrzynski5T. E. Adrian6Department of Physiology, College of Medicine & Health Sciences, UAE University, Al Ain, UAEDepartment of Physiology, College of Medicine & Health Sciences, UAE University, Al Ain, UAEDepartment of Pharmacology, College of Medicine & Health Sciences, UAE University, Al Ain, UAEDepartment of Physiology, College of Medicine & Health Sciences, UAE University, Al Ain, UAEDepartment of Pharmacology, College of Medicine & Health Sciences, UAE University, Al Ain, UAECardiovascular Sciences, University of Manchester, Manchester, UKDepartment of Basic Medical Sciences, Mohammed Bin Rashid University of Medicine & Health Sciences, Dubai, UAEBackground. In vivo experiments in Goto-Kakizaki (GK) type 2 diabetic rats have demonstrated reductions in heart rate from a young age. The expression of genes encoding more than 70 proteins that are associated with the generation and conduction of electrical activity in the GK sinoatrial node (SAN) have been evaluated to further clarify the molecular basis of the low heart rate. Materials and Methods. Heart rate and expression of genes were evaluated with an extracellular electrode and real-time RT-PCR, respectively. Rats aged 12-13 months were employed in these experiments. Results. Isolated spontaneous heart rate was reduced in GK heart (161 ± 12 bpm) compared to controls (229 ± 11 bpm). There were many differences in expression of mRNA, and some of these differences were of particular interest. Compared to control SAN, expression of some genes were downregulated in GK-SAN: gap junction, Gja1 (Cx43), Gja5 (Cx40), Gjc1 (Cx45), and Gjd3 (Cx31.9); cell membrane transport, Trpc1 (TRPC1) and Trpc6 (TRPC6); hyperpolarization-activated cyclic nucleotide-gated channels, Hcn1 (HCN1) and Hcn4 (HCN4); calcium channels, Cacna1d (Cav1.3), Cacna1g (Cav3.1), Cacna1h (Cav3.2), Cacna2d1 (Cavα2δ1), Cacna2d3 (Cavα2δ3), and Cacng4 (Cavγ4); and potassium channels, Kcna2 (Kv1.2), Kcna4 (Kv1.4), Kcna5 (Kv1.5), Kcnb1 (Kv2.1), Kcnd3 (Kv4.3), Kcnj2 (Kir2.1), Kcnk1 (TWIK1), Kcnk5 (K2P5.1), Kcnk6 (TWIK2), and Kcnn2 (SK2) whilst others were upregulated in GK-SAN: Ryr2 (RYR2) and Nppb (BNP). Conclusions. This study provides new insight into the changing expression of genes in the sinoatrial node of diabetic heart.http://dx.doi.org/10.1155/2018/8454078
spellingShingle F. C. Howarth
M. A. Qureshi
P. Jayaprakash
K. Parekh
M. Oz
H. Dobrzynski
T. E. Adrian
The Pattern of mRNA Expression Is Changed in Sinoatrial Node from Goto-Kakizaki Type 2 Diabetic Rat Heart
Journal of Diabetes Research
title The Pattern of mRNA Expression Is Changed in Sinoatrial Node from Goto-Kakizaki Type 2 Diabetic Rat Heart
title_full The Pattern of mRNA Expression Is Changed in Sinoatrial Node from Goto-Kakizaki Type 2 Diabetic Rat Heart
title_fullStr The Pattern of mRNA Expression Is Changed in Sinoatrial Node from Goto-Kakizaki Type 2 Diabetic Rat Heart
title_full_unstemmed The Pattern of mRNA Expression Is Changed in Sinoatrial Node from Goto-Kakizaki Type 2 Diabetic Rat Heart
title_short The Pattern of mRNA Expression Is Changed in Sinoatrial Node from Goto-Kakizaki Type 2 Diabetic Rat Heart
title_sort pattern of mrna expression is changed in sinoatrial node from goto kakizaki type 2 diabetic rat heart
url http://dx.doi.org/10.1155/2018/8454078
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