Ryanodine receptors contribute to cGMP-induced late-phase LTP and CREB phosphorylation in the hippocampus.
We previously found that the nitric oxide (NO)-cGMP-cGMP-dependent protein kinase (PKG) signaling pathway acts in parallel with the cAMP-cAMP-dependent protein kinase (PKA) pathway to produce protein and RNA synthesis-dependent late-phase long-term potentiation (L-LTP) and cAMP response element-binding protein (CREB) phosphorylation in the CA1 region of mouse hippocampus. We have now investigated the possible involvement of a downstream target of PKG, ryanodine receptors. L-LTP can be induced by either multiple-train tetanization, NO or 8-Br-cGMP paired with one-train tetanization, or the cAMP activator forskolin, and all three types of potentiation are accompanied by an increase in phospho-CREB immunofluorescence in the CA1 cell body area. Both the potentiation and the increase in phospho-CREB immunofluorescence induced by multiple-train tetanization or 8-Br-cGMP paired with one-train tetanization are reduced by prolonged perfusion with ryanodine, which blocks Ca(2+) release from ryanodine-sensitive Ca(2+) stores. By contrast, neither the potentiation nor the increase in immunofluorescence induced by forskolin are reduced by depletion of ryanodine and inositol-1,4,5-triphosphate (IP3)-sensitive Ca(2+) stores. These results suggest that NO, cGMP, and PKG cause release of Ca(2+) from ryanodine-sensitive stores, which in turn causes phosphorylation of CREB in parallel with PKA during the induction of L-LTP.
Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Yun-Fei
YF
Lu
Robert D
RD
Hawkins
D000818:Animals; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D004558:Electric Stimulation; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000494:pharmacology; D010766:Phosphorylation; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein; D019837:Ryanodine Receptor Calcium Release Channel; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium