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1 Department of Medicine and Research Center, Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada; Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
2 Department of Medicine and Research Center, Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada
3 Department of Pharmacology and Pharmacotherapy, University of Szeged, and Szeged, Hungary and Research Unit for Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary
4 Masonic Medical Research Laboratories, Utica, New York, USA
* To whom correspondence should be addressed. E-mail: nattel{at}icm.umontreal.ca.
There are important species-specific differences in K+-current profiles and arrhythmia susceptibility, but inter-species comparisons of K+-channel subunit expression are lacking. We quantified ventricular K+-channel 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 ~3-fold values in humans and 20-fold vs. rabbits. MinK protein expression in guinea-pig was >2-fold human and 6-fold rabbit. KvLQT1 mRNA concentration was greatest in man, and protein expression in humans was ~2-fold and ~7-fold values in rabbits and guinea-pigs respectively. ERG1 mRNA was more concentrated in man, but ERG1 protein expression could not be compared across species because of epitope sequence differences. We conclude that important inter-species differences in cardiac K+-channel subunit expression exist and may contribute to: 1) lack of Ito in guinea pig (
-subunit transcription absent in guinea-pig heart); 2) small slow delayed-rectifier current and Torsades de Pointes susceptibility in rabbit (low-level minK expression); 3) large IKs in guinea-pig (strong minK expression).
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