Developmental changes in high-affinity uptake of GABA by cultured neurons

Abstract

High-affinity uptake of [3H]gamma-aminobutyric acid (GABA) was studied in cultures of neonatal rat cortical neurons grown on pre-formed monolayers of non-neuronal (glial) cells. Both the maximum rate (Vmax) and, to a smaller extent, the Km of [3H]GABA uptake increased with time. In addition, in parallel with these changes, 2,4-diaminobutyric acid and cis-3-aminocyclohexane-1-carboxylic acid (ACHC), compounds which are considered typical substrate/inhibitors of GABA uptake in neurons, became progressively stronger inhibitors of [3H]GABA uptake. Consequently, the present results may mean that the studies using uptake of [3H]GABA, [3H]ACHC, or [3H]DABA as a specific marker for GABAergic neurons differentiating during the ontogenetic development of the central nervous system may have to be interpreted with caution.

Distinct, Developmentally Regulated Brain mRNAs Direct the Synthesis of Neurotransmitter Transporters

“…Alterations in Glu, GABA, and Gly transporter mRNA abundance underlie developmental changes in uptake activities Whether assayed in brain slices (Johnston and Davies, 1974), cultured cells (Borg et al, 1980;Balcar et al, 1989), or isolated nerve endings (Coyle and Enna, 1976;Coyle, 1977;Campochiaro and Coyle, 1978;Redburn et al, 1978;Wong and McGeer, 198 affinity, Na+-dependent uptake of Glu, GABA, and Gly exhibit pronounced region-dependent changes in V,,, during rat juvenile development, typically with lesser or no variation in transport K m . Cortical (Hitzemann and Loh, 1978;Wong and McGeer, 1981) and striatal (Campochiaro and Coyle, 1978;Wong and McGeer, 198 1) Glu uptake is detectable at birth, but increases severalfold in the first 2 weeks after birth to reach or exceed adult values.…”