LTP INDUCTION DEPENDENT ON ACTIVATION OF NI2-SENSITIVE VOLTAGE-GATED CALCIUM CHANNELS, BUT NOT NMDA RECEPTORS, IN THE RAT DENTATE GYRUS IN-VITRO()

A N-methyl-D-aspartate receptor (NMDAR)-independent long-term potentia tion (LTP) has been investigated in the dentate gyrus of the hippocamp us in vitro in the presence of the NMDAR antagonist, D-2-amino-phospho nopentanoate (50-100 mu M), at a concentration that completely blocked NMDAR-mediated excitatory postsynaptic currents (EPSCs). LTP of patch -clamped EPSCs was induced by pairing low-frequency evoked EPSCs (1 Hz ) with depolarizing voltage pulses designed to predominately open low- voltage-activated (LVA) Ca2+ channels. Voltage pulses alone induced on ly a short-term potentiation. The LTP was blocked by intracellular app lication of the rapid Ca2+ chelator bis-(O-aminophenoxy)N, N, N', N'-t etraacetic acid, demonstrating that a rise in intracellular Ca2+ is re quired for the NMDAR-independent LTP induction. The NMDAR-independent LTP induction also was blocked by Ni2+ at a low extracellular concentr ation (50 mu M), which is known to strongly block LVA Ca2+ channels. H owever, Ni2+ did not inhibit the NMDAR-dependent LTP induced by high-f requency stimulation (HFS). The NMDAR-independent LTP induction was no t blocked by high concentrations of the L-type Ca2+ channel blocker ni fedipine (10 mu M). The NMDAR-independent LTP was inhibited by the met abotropic glutamate receptor ligand (+)-alpha-methyl-4-carboxyphenylgl ycine . These experiments demonstrate the presence of a NMDAR-independ ent LTP induced by Ca2+ influx via Ni2+-sensitive, nifedipine-insensit ive voltage-gated Ca2+ channels, probably LVA Ca2+ channels. Induction of the NMDAR-independent LTP was inhibited by prior induction of HFS- induced NMDAR-dependent LTP, demonstrating that although the NMDAR-dep endent and NMDAR-independent LTP use a different Ca2+ channel for Ca2 influx, they share a common intracellular pathway.