Ryanodine produces a low frequency stimulation-induced NMDA receptor-independent long-term potentiation in the rat dentate gyrus in vitro.
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.
Wang
Y
Y
Department of Physiology, Trinity College, Dublin, Ireland.
Wu
J
J
Rowan
M J
MJ
Anwyl
R
R
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism; D009532:Nickel / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012430:Ruthenium Red / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology*; D019837:Ryanodine Receptor Calcium Release Channel; D019284:Thapsigargin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002614:Chelating Agents; D018691:Excitatory Amino Acid Antagonists; D009124:Muscle Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D019837:Ryanodine Receptor Calcium Release Channel; D012430:Ruthenium Red; D012433:Ryanodine; D004533:Egtazic Acid; D019284:Thapsigargin; D015763:2-Amino-5-phosphonovalerate; D009532:Nickel; D009543:Nifedipine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium