The Journal of Neurophysiology Vol. 78 No. 5 November 1997, pp. 2574-2581
Copyright ©1997 The American Physiological Society

LTP Induction Dependent on Activation of Ni²⁺-Sensitive Voltage-Gated Calcium Channels, but not NMDA Receptors, in the Rat Dentate Gyrus In Vitro

Yue Wang¹, Michael J. Rowan², and Roger Anwyl¹

¹ Department of Physiology and ² Department of Pharmacology and Therapeutics, Trinity College, Dublin 2, Ireland

Wang, Yue, Michael J. Rowan, and Roger Anwyl. LTP induction dependent on activation of Ni²⁺-sensitive voltage-gated calcium channels, but not NMDA receptors, in the rat dentate gyrus in vitro. J. Neurophysiol. 78: 2574-2581, 1997. A N-methyl-D-aspartate receptor (NMDAR)-independent long-term potentiation (LTP) has been investigated in the dentate gyrus of the hippocampus in vitro in the presence of the NMDAR antagonist, D-2-amino-phosphonopentanoate (50-100 µM), at a concentration thatcompletely 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 only a short-term potentiation. The LTP was blocked by intracellular application of the rapid Ca²⁺ chelator bis-(o-aminophenoxy)-N,N,N,N-tetraacetic acid, demonstrating that a rise in intracellular Ca²⁺ is required for the NMDAR-independent LTP induction. The NMDAR-independent LTP induction also was blocked by Ni²⁺ at a low extracellular concentration (50 µM), which is known to strongly block LVA Ca²⁺ channels. However, Ni²⁺ did not inhibit the NMDAR-dependent LTP induced by high-frequency stimulation (HFS). The NMDAR-independent LTP induction was not blocked by high concentrations of the L-type Ca²⁺ channel blocker nifedipine (10 µM). The NMDAR-independent LTP was inhibited by the metabotropic glutamate receptor ligand (+)--methyl-4-carboxyphenylglycine. These experiments demonstrate the presence of a NMDAR-independent LTP induced by Ca²⁺ influx via Ni²⁺-sensitive, nifedipine-insensitive 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-dependent and NMDAR-independent LTP use a different Ca²⁺ channel for Ca²⁺ influx, they share a common intracellular pathway.

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