Nitric oxide-induced calcium release via ryanodine receptors regulates neuronal function.
Mobilization of intracellular Ca(2+) stores regulates a multitude of cellular functions, but the role of intracellular Ca(2+) release via the ryanodine receptor (RyR) in the brain remains incompletely understood. We found that nitric oxide (NO) directly activates RyRs, which induce Ca(2+) release from intracellular stores of central neurons, and thereby promote prolonged Ca(2+) signalling in the brain. Reversible S-nitrosylation of type 1 RyR (RyR1) triggers this Ca(2+) release. NO-induced Ca(2+) release (NICR) is evoked by type 1 NO synthase-dependent NO production during neural firing, and is essential for cerebellar synaptic plasticity. NO production has also been implicated in pathological conditions including ischaemic brain injury, and our results suggest that NICR is involved in NO-induced neuronal cell death. These findings suggest that NICR via RyR1 plays a regulatory role in the physiological and pathophysiological functions of the brain.
Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. sho-kaki@pharm.kyoto-u.ac.jp
Sho
S
Kakizawa
Toshiko
T
Yamazawa
Yili
Y
Chen
Akihiro
A
Ito
Takashi
T
Murayama
Hideto
H
Oyamada
Nagomi
N
Kurebayashi
Osamu
O
Sato
Masahiko
M
Watanabe
Nozomu
N
Mori
Katsuji
K
Oguchi
Takashi
T
Sakurai
Hiroshi
H
Takeshima
Nobuhito
N
Saito
Masamitsu
M
Iino
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020013:Calcium Signaling / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D066298:In Vitro Techniques; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D018408:Patch-Clamp Techniques; D011993:Recombinant Fusion Proteins / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse