POSTNATAL-DEVELOPMENT OF VOLTAGE-SENSITIVE NA+ CHANNELS IN RAT-BRAIN

Previous studies have shown that mammalian neuronal excitability increases with age, and this excitability may be related to development of Na+ channels. In addition, evidence suggests that Na+ channels are involved in the neuronal response to O-2 deprivation. Because of this, we wished to examine the pharmacologic properties and neuroanatomical distribution of the Na+ channels in newborn brain and as a function of age. In this study, we used ligand-binding techniques and autoradiography with H-3-saxitoxin (STX) to investigate Na+-channel distribution in brains of rats at postnatal days 0, 3, 10, 21, 35, and 120. We found that (1) in each area examined, the Scatchard plots for STX binding were linear in both immature and mature brains in a ligand concentration range of 0.4-64 nM; the slopes, however, were different between areas or ages, with Kd values ranging between 1 and 5 nM; (2) STX-binding density was more than tenfold lower in the rostral brain and cerebellum at birth than in the adult and increased with age; (3) binding density in the newborn brainstem was higher than in other areas such as the cortex and cerebellum, which is opposite to the distribution in the adult; and (d) the brainstem had a different developing pattern with an early-peak density level (P10-21) and a lower adult level. We conclude that (1) there is a major type of STX-binding site in specific brain areas in the developing brain; (2) binding affinity is higher, but density lower, at birth than in the adult, especially in the rostral brain; and (3) developmental profiles of Na+ channels vary among brain areas with an early developmental time table in the brainstem and a later one in the cerebellum and rostral brain. (C) 1994 Wiley-Liss, Inc.