Physiological reports2022; 10(14); e15273; doi: 10.14814/phy2.15273

Cardiac ion channel expression in the equine model – In-silico prediction utilising RNA sequencing data from mixed tissue samples.

Abstract: Understanding cardiomyocyte ion channel expression is crucial to understanding normal cardiac electrophysiology and underlying mechanisms of cardiac pathologies particularly arrhythmias. Hitherto, equine cardiac ion channel expression has rarely been investigated. Therefore, we aim to predict equine cardiac ion channel gene expression. Raw RNAseq data from normal horses from 9 datasets was retrieved from ArrayExpress and European Nucleotide Archive and reanalysed. The normalised (FPKM) read counts for a gene in a mix of tissue were hypothesised to be the average of the expected expression in each tissue weighted by the proportion of the tissue in the mix. The cardiac-specific expression was predicted by estimating the mean expression in each other tissues. To evaluate the performance of the model, predicted gene expression values were compared to the human cardiac gene expression. Cardiac-specific expression could be predicted for 91 ion channels including most expressed Na channels, K channels and Ca -handling proteins. These revealed interesting differences from what would be expected based on human studies. These differences included predominance of Na 1.4 rather than Na 1.5 channel, and RYR1, SERCA1 and CASQ1 rather than RYR2, SERCA2, CASQ2 Ca -handling proteins. Differences in channel expression not only implicate potentially different regulatory mechanisms but also pathological mechanisms of arrhythmogenesis.
Publication Date: 2022-07-27 PubMed ID: 35880716PubMed Central: PMC9316921DOI: 10.14814/phy2.15273Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research aimed to predict the expression of cardiac ion channels in horses, important in studying cardiac health and disease, by analyzing existing RNA sequencing data from mixed tissue samples.

Objective of the Research

  • The research aims to predict the expression of ion channels within the hearts of horses. Understanding this is crucial to studying normal heart function, as well as the underlying mechanisms of heart diseases, especially arrhythmias. There is currently little information on this subject within equine medicine.

Methodology

  • The researchers used raw RNA sequencing data from normal horses that was collected from various previous studies (9 datasets in total). These were sourced from relevant databases such as ArrayExpress and the European Nucleotide Archive.
  • This data was then reinterpreted and normalised based on the average expected gene expression weighted by the tissue proportion in each sample.
  • The researchers used this data to predict the levels of ion channel expression specific to cardiac tissues.

Findings

  • The study was able to predict the cardiac-specific expression of 91 ion channels, which include significant Na channels, K channels, and Ca-handling proteins.
  • The observed results presented interesting findings that differed from what is commonly seen in human studies: the primary expressed Na channel was Na 1.4 (as opposed to Na 1.5), and the key Ca-handling proteins were RYR1, SERCA1, and CASQ1 (as opposed to RYR2, SERCA2 and CASQ2).
  • The different expression levels suggest that there may be unique regulation mechanisms for these ion channels within horses, and understanding this may reveal new insights into the pathways leading to heart disease. The results may also provide important understanding into the mechanisms of arrhythmogenesis, or the development of irregular heart rhythms, in horses.

Conclusion

  • This research provides important revelations about ion channel expression in equine cardiac tissues and begins to fill a gap in the understanding of equine cardiac electrophysiology. The differences in the data in comparison to human studies especially instigate further research into potentially varying regulatory mechanisms in horses. This could have significant implications for the study and treatment of equine cardiac pathologies, such as arrhythmias.

Cite This Article

APA
Premont A, Saadeh K, Edling C, Lewis R, Marr CM, Jeevaratnam K. (2022). Cardiac ion channel expression in the equine model – In-silico prediction utilising RNA sequencing data from mixed tissue samples. Physiol Rep, 10(14), e15273. https://doi.org/10.14814/phy2.15273

Publication

ISSN: 2051-817X
NlmUniqueID: 101607800
Country: United States
Language: English
Volume: 10
Issue: 14
Pages: e15273
PII: e15273

Researcher Affiliations

Premont, Antoine
  • Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.
Saadeh, Khalil
  • Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.
  • School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Edling, Charlotte
  • Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.
Lewis, Rebecca
  • Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.
Marr, Celia M
  • Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.
  • School of Clinical Medicine, University of Cambridge, Cambridge, UK.
  • Rossdales Equine Hospital and Diagnostic Centre, Exning, Suffolk, UK.
Jeevaratnam, Kamalan
  • Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.

MeSH Terms

  • Animals
  • Arrhythmias, Cardiac / genetics
  • Arrhythmias, Cardiac / metabolism
  • Calcium / metabolism
  • Horses / genetics
  • Humans
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Myocytes, Cardiac / metabolism
  • RNA
  • Sequence Analysis, RNA

Conflict of Interest Statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

References

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