Expression pattern of neuronal and skeletal muscle voltage-gated Na+ channels in the developing mouse heart

Volker Haufe, Juan A. Camacho, Robert Dumaine, Bernd Günther, Christian Bollensdorff, Gisela Segond von Banchet, Klaus Benndorf, Thomas Zimmer

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Abstract

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 (INa). Using competitive and real-time RT-PCR we investigated the transcription of six Na+ channels (Nav1.1-Nav1.6) and the β1 subunit during mouse heart development. Nav1.5 was predominantly expressed in the adult heart, whereas the splice variant Nav1.5a was the major Na+ channel isoform in embryonic hearts. The TTX-resistant Na+ channel transcripts (Nav1.5 and Nav1.5a) increased 1.7-fold during postnatal development. Transcripts encoding TTX-sensitive Na+ channels (Nav1.1-Nav1.4) and the β1 subunit gradually increased up to fourfold from postnatal day (P)1 to P126, while the Nav1.6 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 (Nav1.3 > Nav1.4 > Nav1.2 ≫ Nav1.1 ∼ Nav1.6), and 16% in mRNA from isolated cardiomyocytes (Nav1.4 > Nav1.3 > Nav1.2 > Nav1.1 > Nav1.6). Confocal immunofluorescence on ventricular myocytes suggested that Nav1.1 and Nav1.2 were localized at the intercalated disks and in the t tubules. Nav1.3 labelling predominantly produced a diffuse but strong intracellular signal. Nav1.6 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 INa 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.

Original languageEnglish
Pages (from-to)683-696
Number of pages14
JournalJournal of Physiology
Volume564
Issue number3
DOIs
Publication statusPublished - 1 May 2005
Externally publishedYes

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Skeletal Muscle
Cardiac Myocytes
Messenger RNA
Muscle Cells
Action Potentials
Fluorescent Antibody Technique
Real-Time Polymerase Chain Reaction
Protein Isoforms
Fluorescence
Sodium
Proteins

ASJC Scopus subject areas

  • Physiology

Cite this

Haufe, V., Camacho, J. A., Dumaine, R., Günther, B., Bollensdorff, C., von Banchet, G. S., ... Zimmer, T. (2005). Expression pattern of neuronal and skeletal muscle voltage-gated Na+ channels in the developing mouse heart. Journal of Physiology, 564(3), 683-696. https://doi.org/10.1113/jphysiol.2004.079681

Expression pattern of neuronal and skeletal muscle voltage-gated Na+ channels in the developing mouse heart. / Haufe, Volker; Camacho, Juan A.; Dumaine, Robert; Günther, Bernd; Bollensdorff, Christian; von Banchet, Gisela Segond; Benndorf, Klaus; Zimmer, Thomas.

In: Journal of Physiology, Vol. 564, No. 3, 01.05.2005, p. 683-696.

Research output: Contribution to journalArticle

Haufe, V, Camacho, JA, Dumaine, R, Günther, B, Bollensdorff, C, von Banchet, GS, Benndorf, K & Zimmer, T 2005, 'Expression pattern of neuronal and skeletal muscle voltage-gated Na+ channels in the developing mouse heart', Journal of Physiology, vol. 564, no. 3, pp. 683-696. https://doi.org/10.1113/jphysiol.2004.079681
Haufe, Volker ; Camacho, Juan A. ; Dumaine, Robert ; Günther, Bernd ; Bollensdorff, Christian ; von Banchet, Gisela Segond ; Benndorf, Klaus ; Zimmer, Thomas. / Expression pattern of neuronal and skeletal muscle voltage-gated Na+ channels in the developing mouse heart. In: Journal of Physiology. 2005 ; Vol. 564, No. 3. pp. 683-696.
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