Expression pattern of neuronal and skeletal muscle voltage-gated Na+ channels in the developing mouse heart.
In the mammalian heart, a variety of voltage-gated Na(+) channel transcripts and proteins have been detected. However, little quantitative information is available on the abundance of each transcript during development, or the contribution of TTX-sensitive Na(+) channels to the cardiac sodium current (I(Na)). Using competitive and real-time RT-PCR we investigated the transcription of six Na(+) channels (Na(v)1.1-Na(v)1.6) and the beta1 subunit during mouse heart development. Na(v)1.5 was predominantly expressed in the adult heart, whereas the splice variant Na(v)1.5a was the major Na(+) channel isoform in embryonic hearts. The TTX-resistant Na(+) channel transcripts (Na(v)1.5 and Na(v)1.5a) increased 1.7-fold during postnatal development. Transcripts encoding TTX-sensitive Na(+) channels (Na(v)1.1-Na(v)1.4) and the beta1 subunit gradually increased up to fourfold from postnatal day (P)1 to P126, while the Na(v)1.6 transcript level remained low and constant over the same period. In adults, TTX-sensitive channel mRNA accounted for 30-40% of the channel pool in whole-heart preparations (Na(v)1.3 > Na(v)1.4 > Na(v)1.2 >> Na(v)1.1 approximately Na(v)1.6), and 16% in mRNA from isolated cardiomyocytes (Na(v)1.4 > Na(v)1.3 > Na(v)1.2 > Na(v)1.1 > Na(v)1.6). Confocal immunofluorescence on ventricular myocytes suggested that Na(v)1.1 and Na(v)1.2 were localized at the intercalated disks and in the t tubules. Na(v)1.3 labelling predominantly produced a diffuse but strong intracellular signal. Na(v)1.6 fluorescence was detected only along the Z lines. Electrophysiological recordings showed that TTX-sensitive and TTX-resistant Na(+) channels, respectively, accounted for 8% and 92% of the I(Na) in adult ventricular cardiomyocytes. Our data suggest that neuronal and skeletal muscle Na(+) channels contribute to the action potential of cardiomyocytes in the adult mammalian heart.
Haufe
Volker
V
Friedrich Schiller University, Institute of Physiology II, Teichgraben 8, 07740 Jena, Germany.
Camacho
Juan A
JA
Dumaine
Robert
R
Günther
Bernd
B
Bollensdorff
Christian
C
von Banchet
Gisela Segond
GS
Benndorf
Klaus
K
Zimmer
Thomas
T
D000818:Animals; D002478:Cells, Cultured; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006321:Heart / Q000196:embryology*; D015640:Ion Channel Gating / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000196:embryology* / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009928:Organ Specificity; D015222:Sodium Channels / Q000378:metabolism*; D014018:Tissue Distribution
D015222:Sodium Channels
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