SCHWANN-CELLS MODULATE SODIUM-CHANNEL EXPRESSION IN SPINAL SENSORY NEURONS IN-VITRO

In order to study the factors that govern the expression of sodium cha nnel alpha-, beta 1- and beta 2-subunits, the influence that Schwann c ells (SC) exert in the expression of sodium channels in DRG neurons wa s examined with in situ hybridization, immunocytochemistry, and patch clamp recording. The expression of sodium channel alpha-, beta 1-, and beta 2-subunit mRNAs in DRG neurons isolated from E15 rats cultured i n defined medium in the absence (control) or presence of SC, or in SC- conditioned medium, was examined with isoform-specific riboprobes for sodium channel alpha-subunits I, II, III, NaG, Na6, hNE/PN1, SNS, and beta 1- and beta 2-subunits. DRG neurons cultured in the presence of S C displayed a significant (P < 0.05) increase in the hybridization sig nal for NaG, Na6, SNS, and Na beta 2 mRNAs in comparison to control DR G neurons. In contrast, in SC-conditioned medium, only the hybridizati on signal for SNS mRNA was significantly increased. The upregulation o f sodium channel mRNAs in DRG neurons co-cultured with SC was parallel ed by an increase in sodium channel immunoreactivity of these cells. A n increase in the mean sodium current density in DRG neurons in the pr esence of SC was also observed. These results demonstrate that a SC-de rived factor selectively upregulates sodium channel ct-and p-subunit m RNAs in DRG neurons isolated from E15 rats that is reflected in an inc rease in functional sodium channels in these cells. This culture syste m may allow elucidation of the SC factor(s) that modulate the expressi on of sodium channels in DRG neurons. (C) 1997 Wiley-Liss, Inc.