Molecular diversity of voltage-gated sodium channel alpha subunits expressed in neuronal and non-neuronal excitable cells

• Published in: Neuroscience 2005, Vol.130 (2), p.389-396
• Main Authors: Mechaly, I., Scamps, F., Chabbert, C., Sans, A., Valmier, J.
• Format: Article
• Language: English
• Subjects: Alternative Splicing - genetics; Animals; Biological and medical sciences; Cells, Cultured; Ear and associated structures. Auditory pathways and centers. Hearing. Vocal organ. Phonation. Sound production. Echolocation; Exons - genetics; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - genetics; Hair Cells, Auditory - drug effects; Hair Cells, Auditory - metabolism; hippocampal neurons; Hippocampus - drug effects; Hippocampus - metabolism; Membrane Potentials - genetics; NAV1.6 Voltage-Gated Sodium Channel; Nerve Tissue Proteins - genetics; Neurons - drug effects; Neurons - metabolism; Patch-Clamp Techniques; Protein Isoforms - genetics; Protein Subunits - genetics; Rats; Rats, Sprague-Dawley; Rats, Wistar; RNA, Messenger - metabolism; Saccule and Utricle - drug effects; Saccule and Utricle - metabolism; single cell RT-PCR; Sodium Channels - genetics; sodium current; Vertebrates: nervous system and sense organs; vestibular hair cells
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2004.09.034

In order to investigate the role of molecular diversity of voltage-activated sodium channel α-subunits in excitability of neuronal and non-neuronal cells, we carried out patch-clamp recordings and single-cell RT-PCR on two different types of mammalian excitable cells i.e. hippocampal neurons and non-neuronal utricular epithelial hair cells. In each cell type, multiple different combinations of sodium channel α-subunits exist from cell to cell despite similar sodium current properties. The mRNA isoforms, Nav1.2 and Nav1.6, are the most frequently detected by single cell analysis in the two cell types while Nav1.3 and Nav1.7 are also moderately expressed in embryonic hippocampal neurons and in neonatal utricular hair cells respectively. By investigating the particular alternate splice isoforms of Nav1.6 occurring at the exon 18 of the mouse orthologue SCN8A, we revealed that this subunit co-exist in the two cell types under different alternative spliced isoforms. The expression of non-functional isoforms of Nav1.6 in utricular epithelial hair cells excludes the involvement of this subunit in supporting their excitability. Thus, from a functional point of view, the present results suggest that, at the single cell level, both neuronal and non-neuronal excitable cells expressed different and complex patterns of sodium channel gene transcripts but this diversity alone cannot explain the sodium current properties of these cell types.