SODIUM-CHANNEL ALPHA-SUBUNIT MESSENGER-RNAS-I, MESSENGER-RNAS-II, MESSENGER-RNAS-III, NAG, NA6 AND HNE (PN1) - DIFFERENT EXPRESSION PATTERNS IN DEVELOPING RAT NERVOUS-SYSTEM

The expression of sodium channel alpha-subunit mRNAs I, II, III, NaG, Na6 and hNE (PN1) was examined in developing (E17-P30) hippocampus, ce rebellum, spinal cord and dorsal root ganglia using non-isotopic in si tu hybridization cytochemistry. The results showed distinct patterns o f expression for each of the sodium channel mRNAs with maturation of t he nervous system. Tn the hippocampus, sodium channel mRNA I was not d etected at any developmental time, while mRNA II showed increasing hyb ridization signal between E17 and P30. Sodium channel mRNA III was mor e prevalent at late embryonic and early postnatal times, and was barel y detectable at P30. The transcript for NaG showed transient expressio n between P2 and P15, being expressed at low levels at E17 and not bei ng detectable at P30. Sodium channel mRNA Na6 exhibited a high level o f expression between E17 and P15 in the hippocampal formation, with an attenuation of the signal by P30. hNE (PN1) mRNA was not detected in the hippocampus at any time examined. In the cerebellum, sodium channe l mRNA I was not detected at E17 or P2, but became detectable in Purki nje cells at P15 and continued to show a low level of expression in th ese cells at P30. mRNA I was not detected at any time examined in gran ule cells of the cerebellum. Sodium channel mRNA II exhibited increasi ng expression in the developing cerebellum and showed increasing signa l in Purkinge cells beginning on P2 and granule cells on P15. Sodium c hannel mRNA III was down-regulated with development in the cerebellum, although mRNA III was readily detected at E17, it was not detected in any layers of the cerebellum by P15. NaG mRNA showed a peak of expres sion at P2, and was present at low levels at E17 and P15 and not detec table at P30. Na6 mRNA was highly expressed in the E17 cerebellum; thi s mRNA was present at high levels in Purkinje cells throughout develop ment, although in granule cells the signal was attenuated at P15-P30. Sodium channel hNE (PN1) mRNA was not detected in the cerebellum at an y time in development. In the spinal cord, sodium channel mRNA I showe d increasing expression beginning at P2 and was highly expressed, part icularly in ventral motor neurons, by P30. Sodium channel II mRNA was detected at all stages of development in the spinal cord; in contrast, mRNA III was detected at E17 and P2, but showed very low levels of ex pression by P30. NaG mRNA exhibited a transient expression in spinal c ord at P2, but was not detectable at E17 and P30. Na6 mRNA was detecta ble at very low levels at E17 and became highly expressed at P2, prior to a reduction of the signal at P15 and P30, hNE (PN1) mRNA was not d etected in the spinal cord at any time in development. In the dorsal r oot ganglia, sodium channel I mRNA hybridization signal was detected i n DRG neurons at P2, with slightly increased levels at P15 and P30. So dium channel II mRNA exhibited a relatively constant, moderate level o f expression at all developmental ages. sodium channel III mRNA was hi ghly expressed in DRG neurons at E17 but was down-regulated with furth er development so that it was not detectable by P30. NaG mRNA was stro ngly expressed by some DRG neurons at all stages of development from E 17 to P30; in general the level of NaG labelling was greater in larger neurons than in smaller neurons. Na6 mRNA showed increasing expressio n with development in DRG neurons; at E17, low levels of Na6 mRNA were detected and by P15 to P30 high levels of expression were present in some neurons. hNE (PN1) mRNA was present in DRG neurons at P2, and was up-regulated with further development so that by P30 hNE (PN1) was ex pressed in all DRG neurons sizes. These results demonstrate that sodiu m channel alpha-subunit mRNAs I, II, III, NaG, Na6 and hNE (PN1) exhib it distinct spatial and temporal patterns of expression in nervous tis sue, and suggest that the expression of the sodium channel cu-subunits is differentially regulated. The expression of NaG and hNE (PN1) mRNA s in P30 DRG, but not other tissues, may provide a correlate for the p resence, in dorsal root ganglia neurons, of unique sodium currents.