GABAB receptor-mediated effects in human and rat neocortical neurones in vitro

GABA(B) receptor-mediated responses were investigated in human and rat neocortical neurones in vitro by using intracellular recording. Human epileptogenic tissue and cortex from rats were compared for differences related to the cellular mechanisms of hyperexcitability. In both tissues, single stimuli of various intensities were used to compare basic properties of excitatory and inhibitory postsynaptic potentials (EPSP, IPSP). Paired stimuli, causing a decrease of a second IPSP, were used as an index of presynaptic activation of GABA(B) receptors. In neocortical neurones of rats, increasing intensities of stimulation elicited at low intensities (6-8 V) a fairly pure EPSP which was curtailed at higher stimulus intensities (10-14 V) by a GABA(A) receptor mediated IPSP (IPSPA). In all rat neocortical neurones the IPSP, was followed by a late inhibitory component (IPSPB, time to peak about 150 ms) which was eliminated by the GABA(B), receptor antagonists CGP 35348 or CGP 55845A. On average, paired stimuli reduced the amplitude of a second IPSPA to 57% of the first (in the presence of 10 mu M CNQX and 20 mu M D-APV). Paired-pulse depression was only antagonized by CGP 55845A, but not by CGP 35348. The magnitude and time course of paired-pulse depression was markedly enhanced at lower temperatures. In human cortical neurones obtained following epilepsy surgery only low intensity stimuli (4 V) elicited EPSPs. Intermediate to higher stimulus intensities (8-10 V) elicited often all-or-none depolarization shifts or prolonged and increased EPSPs. Few neurones exhibited a sequence of EPSP and IPSPs comparable to that observed in rat neurones. Application of CGP 55845A caused little change in excitability near 150 ms, indicating that the IPSPB is weak. Paired-pulse depression of inhibition was small in most neurones, the second IPSPA was reduced to 82.8% of the first at a 500 ms interval (n = 6). Only two neurones exhibited a paired-pulse depression comparable to rat neurones. The consequences of GABA receptor-mediated paired-pulse depression on neuronal synchronisation are discussed towards the different cellular mechanisms of focal and bilateral synchronous epilepsies. (C) 1999 Elsevier Science Ltd. All rights reserved.