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

Abstract

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.

Cellular and network mechanisms of electrographic seizures

“…Furthermore, intracellular recordings with Cl − filled pipettes did not reveal chloride-mediated effects during 'wave' components of seizures (Timofeev et al 2002b). As to the possibility that GABA B -mediated IPSPs underlie the "wave" component of SW seizures, including QX-314 in the recording pipette to block the G-protein-coupled GABA B -evoked K + current (Deisz et al 1997;Jensen et al 1993) did not significantly affect the hyperpolarization in our experiments ( Fig. 2 B) .…”

Molecular Structure and Physiological Functions of GABABReceptors

“…However, the proposal of presynaptic receptor subtypes based on neurotransmitter release experiments has been open to dispute (336). Electrophysiological and release experiments suggest distinctions between pre-and postsynaptic GABA B receptors as well (65,76,85,88,96,115,262,268,325,352). Accordingly, published half-maximal effective concentrations for baclofen in pharmacological studies vary considerably and range between 100 nM and 100 M ( Table 1).…”

Differential Mechanisms of CRF1 and CRF2 Receptor Functions in the Amygdala in Pain-Related Synaptic Facilitation and Behavior

“…Next we measured the effects of astressin-2B on excitatory and inhibitory transmission in slices from arthritic rats while blocking either postsynaptic GABA A receptors with bicuculline or presynaptic GABA B receptors with CGP35348 (Olpe et al, 1990;Pitler and Alger, 1994;Deisz et al, 1997;Porter and Nieves, 2004). GABA B receptors can serve as presynaptic heteroreceptors on glutamatergic terminals in which they inhibit voltagedependent Ca 2ϩ channels and thus presynaptic calcium influx to decrease glutamate release (Misgeld et al, 1995;Wu and Saggau, 1997;Porter and Nieves, 2004;Potes et al, 2006).…”