Comparative distribution of voltage-gated sodium channel proteins in humanbrain

Antisera directed against unique peptide regions from each of the human bra in voltage-gated sodium channel cr subunits were generated. In immunoblots these were found to be highly specific for the corresponding recombinant po lypeptides and to recognise the native holoprotein in human brain membrane preparations. These antisera were used to perform a comparative immunohisto chemical distribution analysis of all four brain sodium channel subtypes in selected human CNS regions. Distinct but heterogeneous distribution patter ns were observed for each of the alpha subunits. In general, these were com plimentary to that previously shown for the corresponding human mRNAs. A hi gh degree of conservation with respect to the distribution found in rat was also evident. The human a subunit proteins exhibited distinct subcellular localisation patterns. Types I, m and VI immunoreactivity was predominantly in neuronal cell bodies and proximal processes, whereas type II was concen trated along axons. This is similar to rat brain and suggests the different the sodium channel subtypes have distinct functions which are highly conse rved between human and rodents. A notable difference was that the type m pr otein was detected in all human brain regions examined, unlike in rat brain where expression in adults is very restricted. Also in contrast to rat bra in, the human type VI protein was not detected in axons of unmyelinated neu rons. These differences may reflect true species variation and could have i mportant implications for understanding the function of the sodium channel subtypes and their roles in human disease. (C) 2001 Elsevier Science B;V. A ll rights reserved.