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 beta1.1 and Na beta2.1 and the novel, recently cloned subunit, beta3. 2. In situ hybridisation studies demonstrated high levels of Nav1.2, Nav1.3 , Nav1.6 and beta3 mRNA at embryonic stages whilst Na beta1.1 and Na beta2. 1 mRNA was absent throughout this period. 3. Na beta1.1 and Na beta2.1 expression occurred after postnatal day 3 (P3) , increasing steadily in most. brain regions until adulthood. beta3 express ion differentially decreased after P3 in certain areas but remained high in the hippocampus and striatum. 4. Emulsion-dipped slides showed co-localisation of beta3 with Nav1.3 mRNA in areas of the CNS suggesting that these subunits may be capable of functi onal interaction. 5. Co-expression in Xenopus oocytes revealed that. beta3 could modify the p roperties of Nav1.3; beta3 changed the equilibrium of Nav1.3 between the fa st, and slow gating modes and caused a negative shift in the voltage depend ence of activation and inactivation. 6. In conclusion, beta3 is shown to be the predominant beta subunit express ed during development and is capable of modulating the kinetic properties o f the embryonic Nav1.3 subunit. These findings provide new information rega rding the nature and properties of voltage-gated sodium channels during dev elopment.