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The current electrophysiological study investigated the functional roles of high- and low-voltage-activated Ca 2+  channel subtypes on glutamatergic small mossy fiber nerve terminals (SMFTs) that synapse onto rat hippocampal CA3 neurons. Experiments combining both the “synapse bouton” preparation and single-pulse focal stimulation technique were performed using the conventional whole cell patch configuration under voltage-clamp conditions. Nifedipine, at a high concentration, and BAY K 8644 inhibited and facilitated the glutamatergic excitatory postsynaptic currents (eEPSCs) that were evoked by 0.2-Hz stimulation, respectively. However, these drugs had no effects on spontaneous EPSCs (sEPSCs). Following the use of a high stimulation frequency of 3 Hz, however, nifedipine markedly inhibited eEPSCs at the low concentration of 0.3 µM. Moreover, ω-conotoxin GVIA and ω-agatoxin IVA significantly inhibited both sEPSCs and eEPSCs. Furthermore, SNX-482 slightly inhibited eEPSCs. R(−)-efonidipine had no effects on either sEPSCs or eEPSCs. It was concluded that glutamate release from SMFTs depends largely on Ca 2+  entry through N- and P/Q-type Ca 2+  channels and, to a lesser extent, on R-type Ca 2+  channels. The contribution of L-type Ca 2+  channels to eEPSCs was small at low-firing SMFTs but more significant at high-firing SMFTs. T-type Ca 2+  channels did not appear to be involved in neurotransmission at SMFTs.    NEW &amp; NOTEWORTHY Action potential-evoked glutamate release from small mossy fiber nerve terminals (SMFTs) that synapse onto rat hippocampal CA3 neurons is regulated by high-threshold but not low-threshold Ca 2+  channel subtypes. The functional contribution mainly depends on N- and P/Q-type Ca 2+  channels and, to a lesser extent, on R-type Ca 2+  channels. However, in SMFTs stimulated at a high 3-Hz frequency, L-type Ca 2+  channels contributed significantly to the currents. The present results are consistent with previous findings from fluorometric studies of large mossy fiber boutons.

Calcium channel subtypes on glutamatergic mossy fiber terminals synapsing onto rat hippocampal CA3 neurons