NDLI: Requirement of neuronal- and cardiac-type sodium channels for murine sinoatrial node pacemaking

Content Provider	PubMed Central
Author	Lei, Ming Jones, Sandra A. Liu, Jie Lancaster, Matthew K. Fung, Simon S-m Dobrzynski, Halina Patrizia, Camelliti Maier, Sebastian K. G. Noble, Denis Boyett, Mark R.
Copyright Year	2004
Abstract	The majority of Na+ channels in the heart are composed of the tetrodotoxin (TTX)-resistant (K D, 2–6 μm) Nav1.5 isoform; however, recently it has been shown that TTX-sensitive (K D, 1–10 nm) neuronal Na+ channel isoforms (Nav1.1, Nav1.3 and Nav1.6) are also present and functionally important in the myocytes of the ventricles and the sinoatrial (SA) node. In the present study, in mouse SA node pacemaker cells, we investigated Na+ currents under physiological conditions and the expression of cardiac and neuronal Na+ channel isoforms. We identified two distinct Na+ current components, TTX resistant and TTX sensitive. At 37°C, TTX-resistant i Na and TTX-sensitive i Na started to activate at ∼−70 and ∼−60 mV, and peaked at −30 and −10 mV, with a current density of 22 ± 3 and 18 ± 1 pA pF−1, respectively. TTX-sensitive i Na inactivated at more positive potentials as compared to TTX-resistant i Na. Using action potential clamp, TTX-sensitive i Na was observed to activate late during the pacemaker potential. Using immunocytochemistry and confocal microscopy, different distributions of the TTX-resistant cardiac isoform, Nav1.5, and the TTX-sensitive neuronal isoform, Nav1.1, were observed: Nav1.5 was absent from the centre of the SA node, but present in the periphery of the SA node, whereas Nav1.1 was present throughout the SA node. Nanomolar concentrations (10 or 100 nm) of TTX, which block TTX-sensitive i Na, slowed pacemaking in both intact SA node preparations and isolated SA node cells without a significant effect on SA node conduction. In contrast, micromolar concentrations (1–30 μm) of TTX, which block TTX-resistant i Na as well as TTX-sensitive i Na, slowed both pacemaking and SA node conduction. It is concluded that two Na+ channel isoforms are important for the functioning of the SA node: neuronal (putative Nav1.1) and cardiac Nav1.5 isoforms are involved in pacemaking, although the cardiac Nav1.5 isoform alone is involved in the propagation of the action potential from the SA node to the surrounding atrial muscle.
Related Links	http://dx.doi.org/10.1113/jphysiol.2004.068643
Ending Page	848
Page Count	14
Starting Page	835
File Format	PDF
ISSN	00223751
e-ISSN	14697793
Journal	The Journal of Physiology
Issue Number	Pt 3
Volume Number	559
Language	English
Publisher	Blackwell Science Inc
Publisher Date	2004-09-01
Access Restriction	Open
Rights Holder	Blackwell Science Inc
Subject Keyword	Physiology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Physiology Sports Science

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