Future directions in sodium channel research.

Although the human genome comprises approximately 25,000 genes, the number of functional proteins expressed may be massively amplified by the production of splice variants. For example, the single Drosophila gene Dscam has 38,016 possible alternatively spliced forms [1]. Most estimates suggest that more than 40% of mammalian genes are alternatively spliced, and voltage-gated sodium channels are members of this set. From the earliest molecular characterisation of sodium channels, it has been clear that different isoforms may be expressed in development. Studies in insects have given insights into the regulation of expression of sodium channel genes and provided clear evidence that alternatively spliced isoforms may have distinct functional properties. Insect sodium channels are instructive because they have been shown to undergo developmental regulation of splice variants, RNA editing and to display functional diversity of splice variants. Such events may also occur in mammals. Specific pharmacological manipulation of sodium channel isoforms is clearly a challenging route to understanding function. This chapter focuses on the genetics of sodium channel expression, and how manipulating gene expression in transgenic mice will continue to provide useful insights into the specialised roles of sodium channel subtypes.