PHARMACOLOGICAL PROPERTIES OF FETAL-RAT HIPPOCAMPAL GABA(A) RECEPTORS

Cells were cultured from embryonic (E) day 17 and 19 rat hippocampal tissues for one or more days in serum-supplemented growth medium. Intracellular recordings in the whole-eel configuration were made at room temperature. GABA(A) receptor agonists were applied by pressure pulses from closely positioned pipettes. Most of the cells recorded under these conditions responded to one or another ligand. When the equilibrium potential for Cl- was set near 0 mV, current responses to GABA and other GABA(A) receptor agonists reversed polarity near 0 mV, suggesting a dominant role for Cl- ions in the response. Many cells also responded to the general anesthetics (-)pentobarbital and alfaxalone (3 alpha-hydroxy-5 alpha-pregnane-11,20-dione). Micromolar concentrations of these drugs, like the transmitter GABA, elicited membrane current responses that reversed near 0 mV. Sequential exposure of individual neurons to both anesthetics revealed sensitivity to one but not the other agent as well as some responding to both. These results indicate: (1) the GABA(A) receptor function emerges pre-natally in rat hippocampal neurons; (2) barbiturates can have several sites for binding to in GABA(A) receptor complexes.