Developmental expression of the novel voltage-gated sodium channel auxiliary subunit beta 3, in rat CNS

* 1 We have compared the mRNA distribution of sodium channel alpha subunits known to be expressed during development with the known auxiliary subunits Na beta 1.1 and Na beta 2.1 and the novel, recently cloned subunit, beta 3. * 2 In situ hybridisation studies demonstrated high levels of Nav1.2, Nav1.3, Nav1.6 and beta 3 mRNA at embryonic stages whilst Na beta 1.1 and Na beta 2.1 mRNA was absent throughout this period. * 3 Na beta 1.1 and Na beta 2.1 expression occurred after postnatal day 3 (P3), increasing steadily in most brain regions until adulthood. beta 3 expression differentially decreased after P3 in certain areas but remained high in the hippocampus and striatum. * 4 Emulsion-dipped slides showed co-localisation of beta 3 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 beta 3 could modify the properties of Nav1.3; beta 3 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, beta 3 is shown to be the predominant beta 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.