Presynaptic and postsynaptic GABAB receptors of neocortical neurons of the rat in vitro: differences in pharmacology and ionic mechanisms.

The properties of pre- and postsynaptic GABAB receptors were investigated with intracellular recordings from rat neocortical neurons in vitro. An antagonist of the GABAB receptor (CGP 35348) and ions or drugs interfering with GABAB receptor-mediated K+ conductance (Ba2+, QX 314) were employed to delineate possible differences. CGP 35348 reduced the conductance of the late inhibitory postsynaptic potential (IPSPB) in a dose-dependent manner. Neither the early GABAA receptor-mediated inhibitory postsynaptic potential (IPSPA), nor resting membrane potential or direct excitability, were consistently affected by CGP 35348. Bath application of 100 mumol/l Ba2+ decreased IPSPB conductance to about 40% and increased IPSPA conductance to 130% of control. The depression of a second IPSP by a pair of stimuli (paired pulse depression, or PPD) was used as an index for presynaptic GABAB receptor activation. Neither CGP 35348 nor Ba2+ exerted significant effects on the PPD at intervals of 400 msec. The dependence of PPD on the latency of the interval of the stimulus pair was investigated after intracellular applicatio of QX 314 had virtually abolished the IPSPB. Decreasing the stimulus interval from 500 msec to 100 msec revealed a stronger depression of the second IPSPA. Application of CGP 35348 alleviated PPD for stimulus intervals below 300 msec. The data indicate a distinct pharmacological difference between pre- and postsynaptic GABAB receptors. Moreover, we suggest that two temporally distinct presynaptic GABAB receptor effects contribute to PPD: a short-lasting effect, sensitive to CGP 35348, and a long-lasting effect, insensitive to CGP 35348. The latter is insensitive to Ba2+, implying that this component is not associated with a K+ conductance mechanism.