Molecular basis of species-specific expression of repolarizing K + currents in the heart

Stephen Zicha, Isaac Moss, Bruce Allen, A. Varró, J. Papp, Robert Dumaine, Charles Antzelevich, Stanley Nattel

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

There are important species-specific-differences in K+ current profiles and arrhythmia susceptibility, but interspecies comparisons of K + channel subunit expression are lacking. We quantified voltage-gated K+ channel (Kv) subunit mRNA and protein in rabbits, guinea pigs, and humans. Kv1.4, Kv4.2, and Kv4.3 mRNA was present in rabbits but undetectable in guinea pigs. MinK mRNA concentration in guinea pigs was almost threefold greater versus humans and 20-fold versus rabbits. MinK protein expression in guinea pigs was almost twofold that in humans and sixfold that in rabbits. KvLQT1 mRNA concentration was greatest in humans, and protein expression in humans was increased by ∼2- and ∼7-fold compared with values in rabbits and guinea pigs, respectively. The ether-a-go-go-related gene (ERG1) mRNA was more concentrated in humans, but ERG1 protein expression could not be compared across species because of epitope sequence differences. We conclude that important interspecies differences in cardiac K+ channel subunit expression exist and may contribute to the following: 1) lack of a transient outward current in the guinea pig (α-subunit transcription absent in the guinea pig heart); 2) small slow delayed rectifier current and torsades de pointes susceptibility in the rabbit (low-level minK expression); and 3) large slow component of the delayed rectifier current in the guinea pig (strong minK expression).

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number4 54-4
Publication statusPublished - Oct 1 2003

Fingerprint

Guinea Pigs
Mink
Rabbits
Messenger RNA
Voltage-Gated Potassium Channels
Torsades de Pointes
Proteins
Protein Subunits
Ether
Cardiac Arrhythmias
Epitopes
Genes

Keywords

  • Antiarrythmic drugs
  • Arrhythmia
  • ECG
  • Electrophysiology
  • Ion channels
  • Proarrhythmia

ASJC Scopus subject areas

  • Physiology

Cite this

Molecular basis of species-specific expression of repolarizing K + currents in the heart. / Zicha, Stephen; Moss, Isaac; Allen, Bruce; Varró, A.; Papp, J.; Dumaine, Robert; Antzelevich, Charles; Nattel, Stanley.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 285, No. 4 54-4, 01.10.2003.

Research output: Contribution to journalArticle

Zicha, Stephen ; Moss, Isaac ; Allen, Bruce ; Varró, A. ; Papp, J. ; Dumaine, Robert ; Antzelevich, Charles ; Nattel, Stanley. / Molecular basis of species-specific expression of repolarizing K + currents in the heart. In: American Journal of Physiology - Heart and Circulatory Physiology. 2003 ; Vol. 285, No. 4 54-4.
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