Developmental expression of the novel voltage‐gated sodium channel auxiliary subunit β3, in rat CNS

Abstract

1. We have compared the mRNA distribution of sodium channel alpha subunits known to be expressed during development with the known auxiliary subunits Nab1.1 and Nab2.1 and the novel, recently cloned subunit, b3. 2.In situ hybridisation studies demonstrated high levels of Nav1.2, Nav1.3, Nav1.6 and b3 mRNA at embryonic stages whilst Nab1.1 and Nab2.1 mRNA was absent throughout this period.3. Nab1.1 and Nab2.1 expression occurred after postnatal day 3 (P3), increasing steadily in most brain regions until adulthood. b3 expression differentially decreased after P3 in certain areas but remained high in the hippocampus and striatum.4. Emulsion-dipped slides showed co-localisation of b3 with Nav1.3 mRNA in areas of the CNS suggesting that these subunits may be capable of functional interaction.5. Co-expression in Xenopus oocytes revealed that b3 could modify the properties of Nav1.3; b3 changed the equilibrium of Nav1.3 between the fast and slow gating modes and caused a negative shift in the voltage dependence of activation and inactivation.6. In conclusion, b3 is shown to be the predominant b subunit expressed during development and is capable of modulating the kinetic properties of the embryonic Nav1.3 subunit. These findings provide new information regarding the nature and properties of voltage-gated sodium channels during development.

Sodium Channel β1 Subunits Promote Neurite Outgrowth in Cerebellar Granule Neurons

“…The observation that ␤2 reduces neurite extension may be related to its homology to the third Ig loop and juxtamembrane region of F3/contactin, an IGSF CAM capable of strong neurite growth inhibition in monolayer assays (6,31). Whereas mRNA for ␤2 is found within the molecular layer of the cerebellum in adult rats, in situ hybridization studies as well as the present results indicate that P14 -P21 GFAP positive cells, such as Bergmann glia, are devoid of detectable ␤2 expression (18,32). We suggest that ␤1 and ␤2 may act in an antagonistic manner if presented as substrates to the same neuronal cell.…”

“…␤1 and ␤2 mRNAs are expressed as early as P1 in brain. Although ␤1 and ␤2 mRNA expression is initially low in cerebellum, their expression is more robust from P14 through adulthood (18). ␤3 mRNA expression is detected in brain as early as embryonic day 10.…”

“…In situ hybridization studies have suggested that ␤1 mRNA is present in the molecular layer of the cerebellum from P14 through adulthood in rats (18). If sodium channel ␤1 subunits were expressed on Bergmann glial plasma membranes or on the plasma membranes of adjacent granule or Purkinje neurons, then they might serve as in vivo equivalents of the ␤1-transfected fibroblast monolayers used in our co-culture system.…”

“…␤3 mRNA expression is detected in brain as early as embryonic day 10. ␤3 then decreases in brain after P3 in certain areas (including the cerebellum) but remains high in the hippocampus and striatum (18). In adult rats, ␤4 mRNA is expressed in the cerebral cortex, cerebellar purkinje cells, hippocampus, caudate putamen, and globus pallidus (19).…”

Production of Resurgent Current in NaV1.6-Null Purkinje Neurons by Slowing Sodium Channel Inactivation with β-Pompilidotoxin

“…The small resurgent current that remains in med cells suggests that the other sodium channels expressed by Purkinje cells, Na V 1.1 and Na V 1.2 (Felts et al, 1997;Vega-Saenz de Miera et al, 1997;Shah et al, 2001), may bind the putative open-channel blocker, although relatively weakly. The question arises, therefore, of what factors regulate the sensitivity of the different ␣ subunits to open-channel block, thereby controlling their ability to carry resurgent current.…”