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. 2023 Jan 1;27(1):85-94.
doi: 10.4196/kjpp.2023.27.1.85.

Age-dependent expression of ion channel genes in rat

Sung-Cherl Jung  1 , Tong Zhou  2 , Eun-A Ko  1
Affiliations

Age-dependent expression of ion channel genes in rat

Sung-Cherl Jung et al. Korean J Physiol Pharmacol. .

Abstract

Ion channels regulate a large number of cellular functions and their functional role in many diseases makes them potential therapeutic targets. Given their diverse distribution across multiple organs, the roles of ion channels, particularly in age-associated transcriptomic changes in specific organs, are yet to be fully revealed. Using RNA-seq data, we investigated the rat transcriptomic profiles of ion channel genes across 11 organs/tissues and 4 developmental stages in both sexes of Fischer 344 rats and identify tissue-specific and age-dependent changes in ion channel gene expression. Organ-enriched ion channel genes were identified. In particular, the brain showed higher tissue-specificity of ion channel genes, including Gabrd, Gabra6, Gabrg2, Grin2a, and Grin2b. Notably, age-dependent changes in ion channel gene expression were prominently observed in the thymus, including in Aqp1, Clcn4, Hvcn1, Itpr1, Kcng2, Kcnj11, Kcnn3, and Trpm2. Our comprehensive study of ion channel gene expression will serve as a primary resource for biological studies of aging-related diseases caused by abnormal ion channel functions.

Keywords: Aging; Ion channels; RNA-seq; Transcriptome.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1. The “housekeeping” ion channel genes.
For each tissue type, the top 30 ion channel genes with the highest expression were prioritized. The genes highlighted in red are the “housekeeping” ion channel genes, which are among the top 30 list in at least eight tissue types, including Aqp1, Chrna7, Clcn3, Gja1, Itpr1, Itpr2, Mip, Orai1, P2rx4, Pkd2, Tpcn1, and Trpm7.
Fig. 2
Fig. 2. Tissue specificity of ion channel gene expression.
(A) PCA of ion channel gene expression. Each dot represents one sample. PC1 stands the first principal component while PC2 is the second principal component. (B) Cumulative distribution of the mean TPM for different organ/tissue types. (C) Histogram of the TSI of the ion channel genes and the other genes. PCA, principal component analysis; TPM, transcripts per million; TSI, tissue specificity index.
Fig. 3
Fig. 3. Map of tissue-specific ion channel genes.
(A) Hierarchical clustering of the ion channel genes. Each green point stands one tissue-specific ion channel gene. Red color represents relatively increased ion channel gene expression whereas blue color represents relatively lower expression. (B) The top tissue-unique ion channel genes. For each tissue type, the top five ion channel genes with the largest fold change in expression relative to the other tissues are listed. Darker red indicates a larger fold change, while lighter red indicates a smaller fold change. Gray indicates non-significant upregulation.
Fig. 4
Fig. 4. Developmental stage-dependent ion channel gene expression.
PCA indicates that the expression of the ion channel genes shows a strong developmental stage-dependent manner. Each dot represents one sample in a given organ/tissue. PC1 stands the first principal component while PC2 is the second principal component. PCA, principal component analysis.
Fig. 5
Fig. 5. Developmental stage-dependent ion channel genes in thymus.
(A) Distribution of the correlation coefficients (ρ) between the ion channel gene expression and age across the 11 organs/tissues. The ρ values were computed using Spearman’s rank correlation test. (B) Cumulative distribution of the ρ values across the 11 tissue types. There are more ion channel genes in thymus with strong positive correlation between expression and age compared with the other organs/tissues. (C) The top eight ion channel genes showing the strongest positive correlation between expression and age (ρ > 0.9) in thymus. TPM, transcripts per million.
See this image and copyright information in PMC

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