Nitric oxide-induced calcium release via ryanodine receptors regulates neuronal function

Nitric oxide-induced calcium release via ryanodine receptors regulates neuronal function

Sho Kakizawa, Toshiko Yamazawa, Yili Chen(陈毅力), Akihiro Ito, Takashi Murayama, Hideto Oyamada, Nagomi Kurebayashi, Osamu Sato, Masahiko Watanabe, Nozomu Mori, Katsuji Oguchi, Takashi Sakurai, Hiroshi Takeshima, Nobuhito Saito and Masamitsu Iino,  浙江大学医学院附属邵逸夫医院神经外科陈毅力

Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

Mobilization of intracellular Ca2t stores regulates a multitude of cellular functions, but the role of intracellular Ca2t release via the ryanodine receptor (RyR) in the brain remains incompletely understood. We found that nitric oxide (NO) directly activates RyRs, which induce Ca2t release from intracellular stores of central neurons, and thereby promote prolonged Ca2t signalling in the brain. Reversible S-nitrosylation of type 1 RyR (RyR1) triggers this Ca2t release. NO-induced Ca2t 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.

The EMBO Journal (2012) 31, 417?428. doi:10.1038/emboj.2011.386; Published online 28 October 2011

Subject Categories: signal transduction; neuroscience

Keywords: calcium; nitric oxide; ryanodine receptor; synapse