Analysis of the kinetics of synaptic inhibition points to a reduction in GABA release in area CA1 of the genetically epileptic mouse, El.

In order to determine whether changes in synaptic inhibition are involved in chronic models of epilepsy, it is necessary to understand the factors which determine the kinetics of fast gamma-aminobutyric acid (GABA)ergic inhibition. For this purpose, we analyzed the decaying phase of isolated inhibitory postsynaptic currents (IPSC) in rats CA1 pyramidal cells. Reduction of GABA release (by reducing [Ca2+]o or paired-pulse stimulation) or blockade of GABA uptake (with tiagabine) led to the conclusion that small changes in the amount of GABA available for postsynaptic binding have little effect on the peak amplitude, but have marked effect on the duration of the IPSC. We then studied isolated GABAA receptor-mediated inhibition in area CA1 of the El mouse strain, which is genetically predisposed to epilepsy. Results were compared with the non-epileptogenic mother strain, ddY. Inhibitory postsynaptic potentials (IPSPs) in El mice (IPSPEl) were not significantly different in amplitude of those from ddY mice (IPSPddY). However, the rise-time and duration of IPSPEl were respectively about 25% and 50% shorter than those of IPSPddY. With appropriate pharmacological manipulation of GABA release or uptake, IPSPEl could be made to resemble the IPSPddY and vice versa. It is concluded that the synaptic release of GABA in area CA1 of the El mouse is decreased compared to that of the ddY mouse.