Large-scale analysis of ion channel gene expression in the mouse heart during perinatal development

Physiol Genomics. 2007 Feb 12;28(3):273-83. doi: 10.1152/physiolgenomics.00163.2006. Epub 2006 Sep 19.

Abstract

The immature and mature heart differ from each other in terms of excitability, action potential properties, contractility, and relaxation. This includes upregulation of repolarizing K(+) currents, an enhanced inward rectifier K(+) (Kir) current, and changes in Ca(2+), Na(+), and Cl(-) currents. At the molecular level, the developmental regulation of ion channels is scantily described. Using a large-scale real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay, we performed a comprehensive analysis of ion channel transcript expression during perinatal development in the embryonic (embryonic day 17.5), neonatal (postnatal days 1-2), and adult Swiss-Webster mouse hearts. These data are compared with publicly available microarray data sets (Cardiogenomics project). Developmental mRNA expression for several transcripts was consistent with the published literature. For example, transcripts such as Kir2.1, Kir3.1, Nav1.5, Cav1.2, etc. were upregulated after birth, whereas others [e.g., Ca(2+)-activated K(+) (KCa)2.3 and minK] were downregulated. Cl(-) channel transcripts were expressed at higher levels in immature heart, particularly those that are activated by intracellular Ca(2+). Defining alterations in the ion channel transcriptome during perinatal development will lead to a much improved understanding of the electrophysiological alterations occurring in the heart after birth. Our study may have important repercussions in understanding the mechanisms and consequences of electrophysiological alterations in infants and may pave the way for better understanding of clinically relevant events such as congenital abnormalities, cardiomyopathies, heart failure, arrhythmias, cardiac drug therapy, and the sudden infant death syndrome.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / genetics
  • Chloride Channels / genetics
  • Cyclic Nucleotide-Gated Cation Channels
  • Gene Expression
  • Heart / embryology*
  • Heart / growth & development*
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels / genetics*
  • Ion Channels / metabolism
  • Mice
  • Mice, Transgenic
  • Myocardium / metabolism*
  • Potassium Channels / genetics
  • Potassium Channels, Calcium-Activated / genetics
  • Potassium Channels, Inwardly Rectifying / genetics
  • Protein Array Analysis
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sodium Channels / genetics

Substances

  • Calcium Channels
  • Chloride Channels
  • Cyclic Nucleotide-Gated Cation Channels
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels
  • Potassium Channels
  • Potassium Channels, Calcium-Activated
  • Potassium Channels, Inwardly Rectifying
  • RNA, Messenger
  • Sodium Channels