Voltage-gated Na+ channel transcript patterns in the mammalian heart are species-dependent.
In the present study we investigated whether transcription, alternative splicing and developmental regulation of voltage-gated Na(+) channels occur in a species-dependent manner in the mammalian heart. The composition of the Na(+) channel transcript pool including Na(v)1.1-Na(v)1.5 was analysed by RT-PCR in mouse, rat, pig, and human hearts. We found that relative transcript levels of tetrodotoxin (TTX) sensitive channels (Na(v)1.1-Na(v)1.4) decreased with increasing heart size (30% for mouse, 8% for rat, and 4% for pig/human). Considering transcript levels of individual isoforms, human and pig hearts were nearly indistinguishable whereas large differences existed between human and mouse. We also noticed that alternative splicing and age-dependent Na(+) channel expression occurred in a species-dependent manner. Unexpectedly, we even observed gender differences in the cardiac levels of TTX sensitive Na(+) channels in humans. Our data suggest that species differences could underlie published discrepancies on the role of TTX sensitive Na(+) channels in the heart and that the functions of those minor cardiac isoforms in normal and diseased hearts are best studied in larger mammalian animals.
Institute of Physiology II, Friedrich Schiller University, Kollegiengasse 9, 07743 Jena, Germany.
Steve
S
Blechschmidt
Volker
V
Haufe
Klaus
K
Benndorf
Thomas
T
Zimmer
D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005333:Fetus / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics*; D013045:Species Specificity; D034421:Sus scrofa; D014158:Transcription, Genetic; D055815:Young Adult
D017931:DNA Primers; D015222:Sodium Channels