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.
Blechschmidt
Steve
S
Institute of Physiology II, Friedrich Schiller University, Kollegiengasse 9, 07743 Jena, Germany.
Haufe
Volker
V
Benndorf
Klaus
K
Zimmer
Thomas
T
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