Alternative titles; symbols
HGNC Approved Gene Symbol: SCN7A
Cytogenetic location: 2q24.3 Genomic coordinates (GRCh38): 2:166,403,573-166,494,249 (from NCBI)
Voltage-dependent sodium channels are responsible for the initial membrane depolarization that occurs during generation of action potentials in most electrically excitable cells. These ion channel proteins exist as heteromultimeric complexes of a large (approximately 260 kD) alpha subunit and 1 or 2 smaller (approximately 33-38 kD) beta subunits (summary by George et al., 1994).
George et al. (1990) identified a sodium channel alpha-subunit isoform that is expressed in human heart and uterus.
George et al. (1994) assigned the SCN7A gene, which the authors symbolized SCN6A, to chromosome 2 by a PCR-based strategy applied to a human/rodent somatic cell hybrid mapping panel. Confirmation of the localization and regional assignment was achieved using chromosome microdissection-PCR as described by Han et al. (1991). Giesma-banded metaphase chromosomes were dissected with glass needles using a micromanipulator. Microdissected chromosomal fragments were then used as templates in PCR reactions. Thus the assignment of the SCN7A gene to 2q21-q23 was determined. This chromosomal assignment overlaps with that defined for SCN2A (182390) and SCN3A (182391), indicating the existence of a cluster of these genes on 2q.
Watanabe et al. (2000) generated mice in which Scn6a (Scn7a) was knocked-out by insertion of an in-frame lacZ gene. The knockout mice were healthy and fertile. By analyzing targeted mice for lacZ expression, Watanabe et al. (2000) found Scn6a expression in lung, heart, dorsal root ganglia (DRG), and Schwann cells in the peripheral nervous system as well as in neurons and ependymal cells in restricted areas of the CNS. Within the CNS, expression was found in neurons of the circumventricular organs, including the subfornical organ and organum vasculosum laminae terminalis, which are important regions for the control of body fluid ionic balance. Scn6a-deficient mice ingested excessive salt and, under thirst conditions, showed hyperactivity of the neurons in the subfornical organ and organum vasculosum laminae terminalis. Watanabe et al. (2000) proposed that Scn6a functions in the central sensing of body-fluid sodium level and regulation of salt intake behavior.
From studies in Scn6a-deficient mice, Hiyama et al. (2002) concluded that Scn6a is a sodium channel that is sensitive to an increase in the extracellular sodium concentration and is likely to be the sodium-level sensor of body fluids in the brain.
George, A. L., Gellens, M. E., Kallen, R. G., Barchi, R. L. Molecular cloning and chromosomal location of two human muscle voltage-gated sodium channels. Soc. Neurosci. Abst. 16: 184 only, 1990.
George, A. L., Jr., Knops, J. F., Han, J., Finley, W. H., Knittle, T. J., Tamkun, M. M., Brown, G. B. Assignment of a human voltage-dependent sodium channel alpha-subunit gene (SCN6A) to 2q21-q23. Genomics 19: 395-397, 1994. [PubMed: 8188276] [Full Text: https://doi.org/10.1006/geno.1994.1081]
Han, J., Lu, C.-M., Brown, G. B., Rado, T. A. Direct amplification of a single dissected chromosome segment by polymerase chain reaction: a human brain sodium channel gene is on chromosome 2q22-q23. Proc. Nat. Acad. Sci. 88: 335-339, 1991. [PubMed: 1846440] [Full Text: https://doi.org/10.1073/pnas.88.2.335]
Hiyama, T. Y., Watanabe, E., Ono, K., Inenaga, K., Tamkun, M. M., Yoshida, S., Noda, M. Na(x) channel involved in CNS sodium-level sensing. Nature Neurosci. 5: 511-512, 2002. [PubMed: 11992118] [Full Text: https://doi.org/10.1038/nn0602-856]
Watanabe, E., Fujikawa, A., Matsunaga, H., Yasoshima, Y., Sako, N., Yamamoto, T., Saegusa, C., Noda, M. Na(v)2/NaG channel is involved in control of salt-intake behavior in the CNS. J. Neurosci. 20: 7743-7751, 2000. [PubMed: 11027237] [Full Text: https://doi.org/10.1523/JNEUROSCI.20-20-07743.2000]