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Expression pattern of neuronal and skeletal muscle voltage‐gated Na + channels in the developing mouse heart
Author(s) -
Haufe Volker,
Camacho Juan A.,
Dumaine Robert,
Günther Bernd,
Bollensdorff Christian,
Von Banchet Gisela Segond,
Benndorf Klaus,
Zimmer Thomas
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.079681
Subject(s) - sodium channel , microbiology and biotechnology , messenger rna , gene isoform , myocyte , protein subunit , sodium , chemistry , biology , medicine , endocrinology , gene , biochemistry , organic chemistry
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.