Developmental change in GABA(A) receptor desensitization kinetics and its role in synapse function in rat cortical neurons

1. We examined the maturation of GABA(A) receptor synapses in cortical pyra midal neurons cultured from embryonic rats. The decay kinetics of GABA(A), receptor-mediated miniature postsynaptic currents (mPSCs) were compared wit h those of responses evoked by GABA in excised membrane patches. 2. Fast perfusion of 1 or 10 mM GABA on membrane patches evoked currents wi th different desensitizing time courses in young and old neurons. For neuro ns older than 4 days in vitro (DIV), GABA(A) currents had a fast component of desensitization (median approximate to 3 ms) seldom seen in patches from younger neurons. In contrast, mPSCs exhibited a substantial fast component of decay at 2-4 DIV that became more prominent with further development al though the median value of its time constant remained unchanged. 3. The selective alpha 3 subunit positive modulator SB-205384 had no effect on mPSCs at any time in vitro but potentiated extrasynaptic activity. This suggests that synapse maturation does not proceed by a gradual exchange of early embryonic GABA(A) receptor subforms for adult forms. 4. At all ages, the kinetic properties of mPSCs were heterogeneous. This he terogeneity extended to the level of mPSCs from single neurons and may be a normal aspect of synaptic functioning. 5. These results suggest that inhibitory synapses in developing neurons are capable of selectively capturing GABA(A) receptors having fast desensitiza tion kinetics. This functional preference probably reflects the development al turning point from an inwardly looking trophic capacity of embryonic GAB A(A) receptors to a role concerned with information processing.