PMID- 8887781 OWN - NLM STAT- MEDLINE DCOM- 19970219 LR - 20190512 IS - 0022-3751 (Print) IS - 1469-7793 (Electronic) IS - 0022-3751 (Linking) VI - 495 ( Pt 3) IP - Pt 3 DP - 1996 Sep 15 TI - Ryanodine produces a low frequency stimulation-induced NMDA receptor-independent long-term potentiation in the rat dentate gyrus in vitro. PG - 755-67 AB - 1. The induction of long-term potentiation (LTP) was investigated in the rat dentate gyrus in the presence of ryanodine, an agent which is known to selectively bind to the ryanodine receptor (RyR) Ca2+ channels which regulate Ca2+ release from intracellular Ca2+ stores. 2. In control media, high frequency stimulation (HFS) induced LTP, and prolonged low frequency stimulation (LFS) induced long-term depression (LTD), of field excitatory postsynaptic potentials (EPSPs) and patch clamped excitatory postsynaptic currents (EPSCs). 3. In the presence of ryanodine, at a threshold concentration of about 1 microM, HFS-induced LTP was inhibited, whereas LFS (5 Hz, 900 pulses) now induced LTP. 4. The N-methyl-D-aspartate receptor (NMDAR) antagonist D-2-amino-phosphonopentanoate (D-AP5), at both 50 and 200 microM, did not prevent the induction of LTP by 5 Hz LFS in the presence of ryanodine. This demonstrates the NMDAR independence of LTP induction in the presence of ryanodine. Furthermore, D AP5 reversed the block of HFS-induced LTP by ryanodine. 5. The induction of LTP by 5 Hz LFS in the presence of ryanodine was blocked by lowering extracellular Ca2+, or by rapidly buffering intracellular Ca2+ to very low levels with BAPTA. 6. The induction of LTP by 5 Hz LFS was inhibited by the L-type voltage-gated Ca2+ channel blocker nifedipine, and also by Ni2+ a commonly used T type voltage-gated Ca2+ channel blocker. 7. The 5 Hz LFS-induced LTP in the presence of ryanodine was inhibited by the metabotropic glutamate receptor (mGluR) antagonist (+)-alpha-methyl 4-carboxyphenylglycine (MCPG). 8. The 5 Hz LFS-induced LTP in the presence of ryanodine was blocked by Ruthenium Red, an agent known to block RyR channel opening, and also by thapsigargin, an agent known to block-ATP-dependent Ca2+ uptake into endoplasmic reticulum. 9. The results of the present studies emphasize the importance of intracellular Ca2+ stores in the induction of LTP. FAU - Wang, Y AU - Wang Y AD - Department of Physiology, Trinity College, Dublin, Ireland. FAU - Wu, J AU - Wu J FAU - Rowan, M J AU - Rowan MJ FAU - Anwyl, R AU - Anwyl R LA - eng GR - Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Physiol JT - The Journal of physiology JID - 0266262 RN - 0 (Calcium Channel Blockers) RN - 0 (Calcium Channels) RN - 0 (Chelating Agents) RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (Muscle Proteins) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (Ryanodine Receptor Calcium Release Channel) RN - 11103-72-3 (Ruthenium Red) RN - 15662-33-6 (Ryanodine) RN - 526U7A2651 (Egtazic Acid) RN - 67526-95-8 (Thapsigargin) RN - 76726-92-6 (2-Amino-5-phosphonovalerate) RN - 7OV03QG267 (Nickel) RN - I9ZF7L6G2L (Nifedipine) RN - K22DDW77C0 (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) RN - SY7Q814VUP (Calcium) SB - IM MH - 2-Amino-5-phosphonovalerate/pharmacology MH - Animals MH - Calcium/metabolism MH - Calcium Channel Blockers/pharmacology MH - Calcium Channels/drug effects/metabolism MH - Chelating Agents/pharmacology MH - Dentate Gyrus/*drug effects/*physiology MH - Egtazic Acid/analogs & derivatives/pharmacology MH - Electric Stimulation MH - Excitatory Amino Acid Antagonists/pharmacology MH - In Vitro Techniques MH - Long-Term Potentiation/*drug effects MH - Muscle Proteins/drug effects/metabolism MH - Nickel/pharmacology MH - Nifedipine/pharmacology MH - Rats MH - Rats, Wistar MH - Receptors, N-Methyl-D-Aspartate/*metabolism MH - Ruthenium Red/pharmacology MH - Ryanodine/*pharmacology MH - Ryanodine Receptor Calcium Release Channel MH - Thapsigargin/pharmacology PMC - PMC1160780 EDAT- 1996/09/15 00:00 MHDA- 1996/09/15 00:01 PMCR- 1996/09/15 CRDT- 1996/09/15 00:00 PHST- 1996/09/15 00:00 [pubmed] PHST- 1996/09/15 00:01 [medline] PHST- 1996/09/15 00:00 [entrez] PHST- 1996/09/15 00:00 [pmc-release] AID - 10.1113/jphysiol.1996.sp021631 [doi] PST - ppublish SO - J Physiol. 1996 Sep 15;495 ( Pt 3)(Pt 3):755-67. doi: 10.1113/jphysiol.1996.sp021631.