WHOLE-CELL AND SINGLE-CHANNEL PROPERTIES OF A NEW GABA RECEPTOR TRANSIENTLY EXPRESSED IN THE HIPPOCAMPUS

1. The patch-clamp technique was used to characterize, in acutely diss ociated CA3 rat hippocampal neurons, the whole cell and single channel properties of a novel response to gamma-aminobutyric acid (GABA) pres ent only during a restricted period of post natal development. 2. At p ostnatal days 0-10 (P0-P10) both GABA (100 mu M) and isoguvacine (50 m u M) evoked at a holding potential of -50 mV, in symmetrical chloride solution, whole cell inward currents. Bicuculline blocked the response to isoguvacine but only reduced the response to GABA (from 512 +/- 13 7 pA to 60 +/- 13 pA, mean +/- SE). After P12, bicuculline abolished t he response to GABA. 3. The bicuculline insensitive GABA currents were Cl- mediated and antagonized by picrotoxin. The desensitization rate was slower than the conventional bicuculline-sensitive response. The p eak to plateau ratio induced by 0.1 or 1 mM of GABA shifted from 4.6 /- 0.4 and 17.7 +/- 2.6 to 1.5 +/- 0.1 and 3.1 +/- 0.5 in the absence or in the presence of bicuculline, respectively. The recovery from des ensitization was significantly faster for the bicuculline insensitive responses. 4. In excised outside-out patches, GABA (20 mu M) activated , in the presence of bicuculline (100 mu M), single channel currents h aving conductances of 14, 22. and 31 pS. These values were similar to those obtained in the same preparation, in the absence of bicuculline. 5. These findings suggest that this new receptor type, which mediates bicuculline-insensitive responses with slow kinetics, may potentiate the depolarizing action of GABA during a critical period of postnatal development and therefore play a crucial role in synaptogenesis.