REDUCTION IN BIOELECTRIC GABA AND NMDA RESPONSES IN ORGANOTYPIC NEOCORTICAL EXPLANTS BY CHRONIC ELEVATION OF POTASSIUM

Long-term cultures of organotypic neonatal rat neocortex slices were maintained in a serum-free medium supplemented with 25 mM potassium. Such cultures continue to be bioelectrically silent upon return to a 5 mM potassium medium. The absence of responses to pressure ejected gamma-aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) from neurons in treated explants suggests that one consequence of chronic depolarization is a reduction in the density of postsynaptic transmitter receptors. [H-3]Muscimol binding to neocortical membrane preparations shows a large reduction in the binding of this agonist to GABA(A) receptors. These data show that the quantitative expression of at least one neurotransmitter receptor, the GABA(A) receptor, relies on voltage-dependent activity in developing neocortical neurons in vitro.