CALCIUM-DEPENDENCE OF DIFFERENTIATION OF GABA IMMUNOREACTIVITY IN SPINAL NEURONS

The developmental regulation of neurotransmitter synthesis has been ex tensively studied and appears in many cases to depend on electrical ac tivity. The central nervous system of the Xenopus embryo and young lar va is an attractive subject for such studies, since action potentials first elicited from Xenopus spinal neurons at the time of closure of t he neural tube are long in duration and calcium-dependent. Moreover, c ells exhibit spontaneous elevations of intracellular calcium during th is early period as a consequence of calcium influx through voltage-dep endent channels, which induces calcium release from intracellular stor es. Since the early differentiation of Xenopus spinal neurons in disso ciated cell culture parallels development in vivo, we have examined th e maturation of gamma-aminobutyric acid (GABA) immunoreactivity in cul tured neurons and explored its dependence on spontaneous calcium influ x at early stages of development. We find that specific GABA immunorea ctivity develops in spinal neurons in dissociated cell culture with th e same time course previously defined in vivo. Additionally, this proc ess requires calcium influx that occurs spontaneously through voltage- dependent channels. The appearance of GABA immunoreactivity is blocked by transcriptional inhibitors. The early appearance of GABA raises th e possibility that it may play additional roles at early stages of dev elopment. (C) 1993 Wiley-Liss, Inc.