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

• Published in: The Journal of physiology Vol. 564; no. 3; pp. 683 - 696
• Main Authors: Haufe, Volker, Camacho, Juan A., Dumaine, Robert, Günther, Bernd, Bollensdorff, Christian, Von Banchet, Gisela Segond, Benndorf, Klaus, Zimmer, Thomas
• Format: Journal Article
• Language: English
• Published: 9600 Garsington Road , Oxford , OX4 2DQ , UK The Physiological Society 01.05.2005; Blackwell Science Ltd; Blackwell Science Inc
• Subjects: Animals; Cells, Cultured; Gene Expression Profiling - methods; Gene Expression Regulation, Developmental - physiology; Heart - embryology; Ion Channel Gating - physiology; Mice; Mice, Inbred BALB C; Molecular and Genomic Physiology; Muscle, Skeletal - embryology; Muscle, Skeletal - physiology; Myocardium - metabolism; Myocytes, Cardiac - metabolism; Neurons - metabolism; Organ Specificity; Sodium Channels - metabolism; Tissue Distribution
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2004.079681

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 β1 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 β1 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 ∼ 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.