Superoxide-induced potentiation in the hippocampus requires activation of ryanodine receptor type 3 and ERK.
Reactive oxygen species (ROS) are required for the induction of long-term potentiation (LTP) and behave as signaling molecules via redox modifications of target proteins. In particular, superoxide is necessary for induction of LTP, and application of superoxide to hippocampal slices is sufficient to induce LTP in area CA1. Although a rise in postsynaptic intracellular calcium is necessary for LTP induction, superoxide-induced potentiation does not require calcium flux through N-methyl-d-aspartate (NMDA) receptors. Ryanodine receptors (RyRs) mediate calcium-induced calcium release from intracellular stores and have been shown to modulate LTP. In this study, we investigated the highly redox-sensitive RyRs and L-type calcium channels as calcium sources that might mediate superoxide-induced potentiation. In agreement with previous studies of skeletal and cardiac muscle, we found that superoxide enhances activation of RyRs in the mouse hippocampus. We identified a functional coupling between L-type voltage-gated calcium channels and RyRs and identified RyR3, a subtype enriched in area CA1, as the specific isoform required for superoxide-induced potentiation. Superoxide also enhanced the phosphorylation of extracellular signal-regulated kinase (ERK) in area CA1, and ERK was necessary for superoxide-induced potentiation. Thus superoxide-induced potentiation requires the redox targeting of RyR3 and the subsequent activation of ERK.
Huddleston
A Tara
AT
Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Tang
Wei
W
Takeshima
Hiroshi
H
Hamilton
Susan L
SL
Klann
Eric
E
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D016877:Oxidants / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000172:deficiency / Q000502:physiology*; D013481:Superoxides / Q000494:pharmacology*; D019820:Xanthine / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology
D004791:Enzyme Inhibitors; D016877:Oxidants; D019837:Ryanodine Receptor Calcium Release Channel; D013481:Superoxides; D012433:Ryanodine; D019820:Xanthine; D014969:Xanthine Oxidase; D048049:Extracellular Signal-Regulated MAP Kinases