Distribution of voltage-gated sodium channel alpha-subunit and beta-subunit mRNAs in human hippocampal formation, cortex, and cerebellum

The distribution of mRNAs encoding voltage-gated sodium channel alpha subun its (I, II, III, and VI) and beta subunits (beta 1 and beta 2) was studied in selected regions of the human brain by Northern blot and in situ hybridi sation experiments. Northern blot analysis showed that all regions studied exhibited heterogenous expression of sodium channel transcripts. In situ hy bridisation experiments confirmed these findings and revealed a predominant ly neuronal distribution. In the parahippocampal gyrus, subtypes II and VI and the beta-subunit mRNAs exhibited robust expression in the granule cells of the dentate gyrus and pyramidal cell layer of the hippocampus. Subtypes I and LII showed moderate expression in granule cells and low expression i n the pyramidal cell layer. Distinct expression patterns were also observed in the cortical layers of the middle frontal gyrus and in the entorhinal c ortex. In particular, all subtypes exhibited higher levels of expression in cortical layers III, V, and Vf compared with layers I and II. All subtypes were expressed in the granular layer of the cerebellum, whereas specific e xpression of subtypes I, VI, beta 1, and beta 2 mRNAs was observed in Purki nje cells. Subtypes I, VI, and beta 1 mRNAs were expressed, at varying leve ls, in the pyramidal cells of the deep cerebellar nuclei. These data indica te that, as in rat, human brain sodium channel mRNAs have a distinct region al distribution, with individual cell types expressing different compliment s of sodium channels. The differential distribution of sodium channel subty pes suggest that they have distinct roles that are likely to be of paramoun t importance in maintaining the functional heterogeneity of central nervous system neurons. (C) 2000 Wiley-Liss, Inc.