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J Physiol. 1999 May 1;516 ( Pt 3):855-68.

Inositol 1,3,4,5-tetrakisphosphate enhances long-term potentiation by regulating Ca2+ entry in rat hippocampus.

Author information

  • 1Project Group Neuropharmacology, Leibniz Institute for Neurobiology, POB 1860, D-39008 Magdeburg, Germany.

Abstract

1. The effect of inositol 1,3,4,5-tetrakisphosphate (InsP4) on long-term potentiation (LTP) was investigated in the CA1 region of rat hippocampal slices. Intracellular application of InsP4 and EPSP recordings were carried out using the whole-cell configuration. 2. Induction of LTP in the presence of InsP4 (100 microM) resulted in a substantial enhancement of the LTP magnitude compared with control potentiation. Using an intrapipette perfusion system, it was established that application of InsP4 was required during induction of potentiation for this enhancement to occur. An enhancement of LTP was not observed if a non-metabolizable inositol 1,4,5-trisphosphate (InsP3) analogue (2,3-dideoxy-1,4,5-trisphosphate, 100 microM) was applied intracellularly. 3. Current-voltage relations of NMDA receptor-mediated EPSCs were not altered by InsP4 application. The presence of InsP4 was slightly effective in relieving a D-(-)-2-amino-5-phosphonopentanoic acid (D-APV)-induced block of LTP. 4. The peak current amplitude of voltage-gated calcium channels (VGCCs) was increased by InsP4. omega-Conotoxin GVIA inhibited the InsP4-induced LTP facilitation. 5. These data indicate that InsP4 can modify the extracellular Ca2+ entry through upregulation of VGCCs, which may in turn contribute to the observed enhancement of LTP induced by InsP4. 6. To investigate the possible involvement of intracellular Ca2+ release in the facilitatory effect of InsP4 on LTP, different inhibitors of the endoplasmic reticulum-dependent Ca2+ release were applied (heparin, ryanodine, cyclopiazonic acid). The results suggest that InsP4 activates postsynaptic InsP3-dependent Ca2+ release which normally does not contribute to the calcium-induced calcium release-dependent LTP.

PMID:
10200431
[PubMed - indexed for MEDLINE]
PMCID:
PMC2269287
Free PMC Article

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