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Updated: May 6, 2026

Functional Characterization of Endogenously Expressed Human RYR1 Variants
Published on: June 9, 2021
Nitric Oxide-Induced Calcium Release: Activation of Type 1 Ryanodine Receptor, a Calcium Release Channel, through
1Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University , Kyoto , Japan.
Abstract:
Nitric oxide (NO) is a typical gaseous messenger involved in a wide range of biological processes. In our classical knowledge, effects of NO are largely achieved by activation of soluble guanylyl cyclase to form cyclic guanosine-3', 5'-monophosphate. However, emerging evidences have suggested another signaling mechanism mediated by NO: "S-nitrosylation" of target proteins. S-nitrosylation is a covalent addition of an NO group to a cysteine thiol/sulfhydryl (RSH), and categorized into non-enzymatic post-translational modification (PTM) of proteins, contrasted to enzymatic PTM of proteins, such as phosphorylation mediated by various protein kinases. Very recently, we found novel intracellular calcium (Ca(2+)) mobilizing mechanism, NO-induced Ca(2+) release (NICR) in cerebellar Purkinje cells. NICR is mediated by type 1 ryanodine receptor (RyR1), a Ca(2+) release channel expressed in endoplasmic-reticular membrane. Furthermore, NICR is indicated to be dependent on S-nitrosylation of RyR1, and involved in synaptic plasticity in the cerebellum. In this review, molecular mechanisms and functional significance of NICR, as well as non-enzymatic PTM of proteins by gaseous signals, are described.
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