Multiple types of high-voltage-activated Ca2+ channels trigger neurotransmitter release at the mammalian central synapse. Now it is clear that N-type Ca2+ channels contribute to synap-tic transmission at many of CNS synapses. However, it is not known whether presynaptic N-type Ca2+ channels contribute to calcium-dependent paired pulse depression (PPD) medi­ated by GABA release at inhibitory synapses of cultured hippocampal neurons. We studied the sensitivity of GABAergic depression to selective N-type high-voltage-activated Ca2+ channels blocker omega-conotoxin- GVIA (w-CgTx) under dif­ferent calcium concentrations. Evoked inhibitory postsynap-tic currents were studied using patch-clamp technique in whole-cell configuration in postsynaptic neuron and local exteracellular paired - pulse stimulation of single presynaptic axon by rectangular pulse with 0.4 ms duration, the interpulse interval in pair was 150 ms. The present data show that the relationship between eIPSC and extracellular Ca2+ concentration are highly nonlinear. The fraction of N-type Ca2+ channel in calcium-dependent PPD was estimated in presence of w-CgTx (200 nM). The application of w-CgTx did not change nonlinear relationship. It was shown that PPD is qualitatively affected by the extracellular Ca2+ concentration. Lowering external Ca2+ concentration reduced the depression powerfully in presence of w-CgTx than in absence. In addition we found difference between the degree of cooperativity for transmitter release in the presence and absence of the N-type Ca2+ channel blocker. So, at inhibitory synapses in the hippocampus more than one Ca2+ ions act in a cooperative manner to cause release of GABA. After w-CgTx application the degree of cooperativity nH was increased. These results confirm that N-type Ca2+ channels are highly involved in calcium-dependent paired pulse depres­sion at inhibitory synapse in cultured hippocampal neurons.