GABA EXCITES IMMATURE CA3 PYRAMIDAL CELLS THROUGH BICUCULLINE-SENSITIVE AND BICUCULLINE-INSENSITIVE CHLORIDE-DEPENDENT RECEPTORS

Intracellular and patch clamp recording techniques were used to invest igate the role of GABA in immature CA3 hippocampal neurons. During the first postnatal week spontaneous GABA release was detected as spontan eous ongoing synaptic potentials (SPSPs) or giant depolarizing potenti als (GDPs). GDPs were generated at regular intervals and regulated by ionotropic glutamate receptors (GluRs), whereas SPSPs occurred randoml y and were unaffected by ionotropic GluRs. Both GDPs and SPSPs were po sitively modulated by metabotropic GluRs through cyclic AMP-dependent protein kinase. Moreover GABA controlled its own release through GABA( A) and GABA(B) receptors, probably localized on GABAergic nerve termin als. At this developmental stage, GABA depolarized CA3 pyramidal cells through two distinct classes of chloride-permeable receptors: bicucul line sensitive and insensitive, respectively. The bicuculline-insensit ive responses were blocked by picrotoxin in a noncompetitive way. Whol e-cell GABA currents, recorded in the presence of bicuculline, had a s lower desensitization rate and faster recovery from desensitization. I n excised outside-out patches, in the presence of bicuculline, GABA ac tivated single-channel currents with conductances of 14, 22, and 31 pS . These values were similar to those obtained when GABA was applied in the absence of bicuculline. Interestingly, GABA responses obtained in the absence of bicuculline, were sensitive to the blocking effect of zinc, whereas bicuculline-resistant responses were almost unaffected b y this divalent cation. Expression of different subunits in native rec eptors (particularly of the alpha and rho type) may account for the fu nctional differences observed in the present experiments. Activation o f bicuculline-insensitive receptors would strenghten and prolong the d epolarizing action of GABA, thus favoring the entry of calcium through voltage-dependent calcium channels. This calcium signal may be essent ial in promoting stabilization of synaptic contacts during a critical period of postnatal development.