Post-tetanic potentiation of GABAergic IPSCs in cultured rat hippocampal neurones

1. Dual whole-cell patch-clamp recording was used to investigate post-tetan ic potentiation (PTP) of GABAergic IPSCs evoked between pairs of cultured r at hippocampal neurones. Tetanization of the presynaptic neurone at frequen cies (f) ranging from 5 to 100 Hz resulted in PTP of the IPSCs. Maximum PTP had a magnitude of 51.6 % just after the stimulus train, and lasted up to 1 min. PTP was shown to be dependent on the number of stimuli in the train, but independent of f at frequencies greater than or equal to 5 Hz. 2. Blocking postsynaptic GABA(A) receptors with bicuculline during the teta nus did not affect the expression of PTP, showing that it is a presynaptic phenomenon. PTP was strongly affected by changing [Ca2+](o) during the teta nus: PTP was reduced by lowering [Ca2+](o), and increased by high [Ca2+](o) . 3. PTP was still present after presynaptic injection of BAPTA or EGTA, or f ollowing perfusion of the membrane-permeable ester EGTA-tetraacetoxymethyl ester (EGTA AM, 50 mu M). On the other hand, EGTA AM blocked spontaneous, a synchronous IPSCs (asIPSCs), which were often associated with tetanic stimu lation. 4. Tetanic stimulation in the presence of 4-aminopyridine (4-AP), which pro motes presynaptic Ca2+ influx, evoked sustained PTP of IPSCs in half of the neurones tested. 5. The results indicate that PTP at inhibitory GABAergic synapses is relate d to the magnitude of presynaptic Ca2+ influx during the tetanic stimulatio n, leading to an enhanced probability of vesicle release in the post-tetani c period. The increase in [Ca2+](l) occurs despite the presence of high-aff inity exogenous and endogenous intracellular Ca2+ buffers. That PTP of IPSC s depends on the number, and not the frequency, of spikes in the GABAergic neurone is in accordance with a slow clearing of intracellular Ca2+ from th e presynaptic terminals.