Evidence map›Paper›PMID 36574099›Full record

ArticleMolecular and cellular biochemistry2023

Depressed HCN4 function in the type 2 diabetic sinoatrial node.

Sajida Parveen, Paddy H S Cheah, Luke P I Worthington, Roseanna A Smither, Michelle L Munro, Carol T Bussey, Regis R Lamberts, Peter P Jones

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Article in Molecular and cellular biochemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.3field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 8 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Sajida ParveenDepartment of Physiology, School of Biomedical Sciences, and HeartOtago, University of Otago, Dunedin, Otago, New Zealand.
Paddy H S CheahDepartment of Physiology, School of Biomedical Sciences, and HeartOtago, University of Otago, Dunedin, Otago, New Zealand.
Luke P I WorthingtonDepartment of Physiology, School of Biomedical Sciences, and HeartOtago, University of Otago, Dunedin, Otago, New Zealand.
Roseanna A SmitherDepartment of Medicine, School of Medicine and HeartOtago, University of Otago, Dunedin, Otago, New Zealand.
Michelle L MunroDepartment of Physiology, School of Biomedical Sciences, and HeartOtago, University of Otago, Dunedin, Otago, New Zealand.
Carol T BusseyDepartment of Physiology, Faculty of Medical and Health Sciences, Manaaki Mānawa Centre for Heart Research, University of Auckland, Auckland, New Zealand.
Regis R LambertsDepartment of Physiology, School of Biomedical Sciences, and HeartOtago, University of Otago, Dunedin, Otago, New Zealand.
Peter P JonesDepartment of Physiology, School of Biomedical Sciences, and HeartOtago, University of Otago, Dunedin, Otago, New Zealand. pete.jones@otago.ac.nz.
University of Otago · NZUniversity of Auckland · NZ

Funding

Health Research Council of New Zealand 18/232National Heart Foundation of New Zealand 1771National Heart Foundation of New Zealand 1836National Heart Foundation of New Zealand Fellowship 1784
6 · The paper itself

Abstract

Diabetic patients often have impaired heart rate (HR) control. HR is regulated both intrinsically within the sinoatrial node (SAN) and via neuronal input. Previously, we found lower ex vivo HR in type 2 diabetic rat hearts, suggesting impaired HR generation within the SAN. The major driver of pacemaking within the SAN is the activity of hyperpolarisation-activated cyclic nucleotide-gated 4 (HCN(4)) channels. This study aimed to investigate whether the lower intrinsic HR in the type 2 diabetic heart is due to changes in HCN4 function, protein expression and/ or distribution. The intrinsic HR response to HCN4 blockade was determined in isolated Langendorff-perfused hearts of Zucker type 2 Diabetic Fatty (ZDF) rats (DM) and their non-diabetic ZDF littermates (nDM). HCN4 protein expression and membrane localisation were determined using western blot and immunofluorescence, respectively. We found that the intrinsic HR was lower in DM compared to nDM hearts. The change in intrinsic HR in response to HCN4 blockade with ivabradine was diminished in DM hearts, which normalised the intrinsic HR between the groups. HCN4 protein expression was decreased in the SAN of DM compared to nDM controls with no change in the fraction of HCN4 localised to the membrane of SAN cardiomyocytes. The lower intrinsic HR in DM is likely due to decreased HCN4 expression and depressed HCN4 function. Our study provides a novel understanding into the intrinsic mechanisms underlying altered HR control in type 2 diabetes.

Indexed as

Diabetes Mellitus, Type 2Sinoatrial NodeAnimalsHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsMyocytes, CardiacPotassium ChannelsRatsRats, ZuckerHCN4 protein, ratHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsPotassium ChannelsHeart rateSinoatrial nodeType 2 diabetes

Identifiers

PMID36574099
OpenAlexW4312212095

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.