L-type Ca²⁺ channels are thought not to be critical for synaptic transmitter release evoked by low-frequency stimulation, but do in some cases contribute to post-tetanic potentiation (PTP) of evoked release. We have previously shown that L-type channels are present in presynaptic terminals on medial preoptic neurons from rat and here analyse their roles in evoked as well as spontaneous transmission, by perforated-patch recording in brain slices. At low-frequency (0.5 – 2.0 Hz) presynaptic stimulation, the L-type channel blocker calciseptine (100 mM) significantly enhanced GABA_A-receptor- mediated as well as AMPA-receptor-mediated postsynaptic currents, by 317% (n= 6) and 18 5 % (n = 9) respectively (mean S.E.M.). In contrast, the steady frequency of spontaneous GABA-mediated postsynaptic currents (sIPSCs) was not affected by calciseptine. After a 10-s period of high- frequency (50 Hz) stimulation, there was PTP of evoked GABA_A-receptor-mediated postsynaptic currents, but they were only slightly affected by calciseptine. The high- frequency stimulation also induced PTP of the sIPSC frequency. However, after such potentiation, calciseptine significantly reduced the sIPSC frequency, by 2410 % (n = 13). Thus, in MPN neurons, L-type Ca ²⁺ channels may play a role at low- frequency-stimulation and differentially affect evoked and spontaneous transmitter release. We speculate that, at low frequency stimulation, the limited Ca²⁺ entry through L-type channels affects transmission via Ca²⁺-gated K⁺ channels and effects on the membrane potential, whereas at high-frequency stimulation, a more massive Ca²⁺ entry induces more direct potentiating effects on the release machinery.