Copyright © 2004, European Society of Cardiology
Contribution of neuronal sodium channels to the cardiac fast sodium current INa is greater in dog heart Purkinje fibers than in ventricles
aFriedrich Schiller University Jena, Institute of Physiology II, Teichgraben 8, 07740 Jena, Germany
bMasonic Medical Research Laboratory, 2150 Bleecker Street Utica NY 13501, USA
* Corresponding author. Tel.: +315 735 2217; fax: +315 735 5648. Email address: rdumaine{at}mmrl.edu
Objective: To determine the presence and the potential contribution of neuronal sodium channels to dog cardiac function.
Methods: We used a combination of electrophysiological (patch clamp), RT-PCR, biochemical and immunohistochemical techniques to identify and localize neuronal Na+ channels in dog heart and determine their potential contribution to the fast sodium current.
Results: In all cardiac tissues investigated, Nav1.1, Nav1.2 and Nav1.3 transcripts were detected. In immunoblots, we found Nav1.1 and Nav1.2 proteins in the ventricle (V) and in Purkinje fibers (PF). Nav1.3 immunoblots suggested strong proteolytic activity against this isoform in the heart. Nav1.6 was not found in any of the tissues tested. Confocal immunofluorescence on cardiac myocytes showed that Nav1.1 was predominantly localized at the intercalated disks in V and PF and around the nucleus (V). Nav1.2 was only present at the Z lines (V). Consistent with the immunoblot data, an intense but diffuse intracellular staining was observed for Nav1.3. Nav1.6 fluorescence staining was faint and diffuse. Surprisingly, immunoblots indicated the presence of two Navβ2 variants: a 42-kDa protein that co-localized with Nav1.2 at the Z lines in V and a 34-kDa protein that co-localized with Nav1.1 at the intercalated disks in PF. In agreement with the biochemical data, electrophysiological results suggest that neuronal sodium channels generate 10 ± 5% and 22 ± 5% of the peak sodium current in dog ventricle and Purkinje fibers, respectively.
Conclusions: Our results suggest that neuronal NaChs are more abundant in Purkinje fibers than in ventricles, and this suggests a role for them in cardiac conduction.
KEYWORDS Ion channels; Gene expression; Purkinje fibers; Na-channel
Time for primary review 26 days
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