Developmental and regional expression of sodium channel isoform NaCh6 in the rat central nervous system

The sodium channel isoform NaCh6 is abundant in the adult rat brain and is expressed in both neurons and glia (Schaller et al. [1995] J. Neurosci. 15: 3231-3242; Krzemien et al. [2000] J. Comp. Neurol. 20:70-83). With reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization, an d immunolabeling, NaCh6 expression was investigated in the developing rat b rain and spinal cord [embryonic day 15 (E15) through postnatal day 28 (P28) ]. The relative abundance of the four major central nervous system NaCh sub types was quantitated with RT-PCR. In all regions that were investigated (o lfactory bulb, cortex, hippocampus, cerebellum, and spinal cord), each subt ype had a unique pattern of expression. NaCh6 mRNA and protein were not det ected in either brain or spinal cord at E15 and E18 by in situ hybridizatio n and immunohistochemistry. Neurons in the hippocampus, cortex, and olfacto ry bulb began to express NaCh6 mRNA. and protein shortly after birth. The m RNA signal peaked at P7-P14, and protein expression increased as developmen t proceeded. NaCh6 mRNA was detected at P1 in the cerebellum, and a nonunif orm distribution of NaCh6 immunoreactivity in both Purkinje cells and granu le cells was observed by P7-P14. NaCh6 protein was expressed in granule cel ls as soon as they left the proliferative phase and began to migrate. Both NaCh6 mRNA and protein were detected in the spinal cord at P1 and were expr essed clearly at P7 in motor neurons. The time course of appearance of NaCh 6 in postnatal development is consistent with the development of neurologic symptoms in mcd and jolting mice, which have mutations in the mouse orthol og of NaCh6. J. Comp. Neurol. 420:84-97, 2000. (C) 2000 Wiley-Liss, Inc.