Postsynaptic modulation of AMPA receptor-mediated synaptic responses and LTP by the type 3 ryanodine receptor.
The precise function of ryanodine receptors (RyRs) in synaptic transmission is unknown, but three of their subtypes are expressed in the brain. We examined the roleof RyRs in excitatory synaptic transmission in hippocampal slices, using type 3 RyR (RyR3)-deficient mice. The alpha-amino-3-hydroxy-5-methyl-4-isoxozolepropionic acid (AMPA) receptor-mediated basal synaptic responses in the CA1 region of mutant mice were smaller than those of wild-type mice, while there was no difference in N-methyl-d-aspartate receptor-mediated responses, suggesting selective postsynaptic modification of AMPA receptors by RyR3. The expression of synaptic AMPA receptor subunits examined by Western blotting or immunohistochemistry was indistinguishable, suggesting that the smaller AMPA synaptic responses in mutant mice were not due to the reduced number of synaptic AMPA receptors. Although the initial potentiation following tetanic stimulation of afferent fibers was similar, long-term potentiation (LTP) was smaller in mutant mice. There were no differences in presynaptic electrophysiological properties. We thus conclude that RyR3 postsynaptically regulates the properties of AMPA receptors and LTP.
Shimuta
M
M
Department of Physiology, Kobe University School of Medicine, Kobe 650-0017, Japan.
Yoshikawa
M
M
Fukaya
M
M
Watanabe
M
M
Takeshima
H
H
Manabe
T
T
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000172:deficiency* / Q000187:drug effects / Q000235:genetics; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D015763:2-Amino-5-phosphonovalerate; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D019837:Ryanodine Receptor Calcium Release Channel; C104723:glutamate receptor ionotropic, AMPA 3; C104724:glutamate receptor ionotropic, AMPA 4; C104722:glutamate receptor ionotropic, AMPA 2